network model inference: Topics by Science.gov

Sample records for network model inference

Network inference using informative priors.

PubMed

Mukherjee, Sach; Speed, Terence P

2008-09-23

Recent years have seen much interest in the study of systems characterized by multiple interacting components. A class of statistical models called graphical models, in which graphs are used to represent probabilistic relationships between variables, provides a framework for formal inference regarding such systems. In many settings, the object of inference is the network structure itself. This problem of "network inference" is well known to be a challenging one. However, in scientific settings there is very often existing information regarding network connectivity. A natural idea then is to take account of such information during inference. This article addresses the question of incorporating prior information into network inference. We focus on directed models called Bayesian networks, and use Markov chain Monte Carlo to draw samples from posterior distributions over network structures. We introduce prior distributions on graphs capable of capturing information regarding network features including edges, classes of edges, degree distributions, and sparsity. We illustrate our approach in the context of systems biology, applying our methods to network inference in cancer signaling.
Expectation propagation for large scale Bayesian inference of non-linear molecular networks from perturbation data.

PubMed

Narimani, Zahra; Beigy, Hamid; Ahmad, Ashar; Masoudi-Nejad, Ali; Fröhlich, Holger

2017-01-01

Inferring the structure of molecular networks from time series protein or gene expression data provides valuable information about the complex biological processes of the cell. Causal network structure inference has been approached using different methods in the past. Most causal network inference techniques, such as Dynamic Bayesian Networks and ordinary differential equations, are limited by their computational complexity and thus make large scale inference infeasible. This is specifically true if a Bayesian framework is applied in order to deal with the unavoidable uncertainty about the correct model. We devise a novel Bayesian network reverse engineering approach using ordinary differential equations with the ability to include non-linearity. Besides modeling arbitrary, possibly combinatorial and time dependent perturbations with unknown targets, one of our main contributions is the use of Expectation Propagation, an algorithm for approximate Bayesian inference over large scale network structures in short computation time. We further explore the possibility of integrating prior knowledge into network inference. We evaluate the proposed model on DREAM4 and DREAM8 data and find it competitive against several state-of-the-art existing network inference methods.
An algebra-based method for inferring gene regulatory networks.

PubMed

Vera-Licona, Paola; Jarrah, Abdul; Garcia-Puente, Luis David; McGee, John; Laubenbacher, Reinhard

2014-03-26

The inference of gene regulatory networks (GRNs) from experimental observations is at the heart of systems biology. This includes the inference of both the network topology and its dynamics. While there are many algorithms available to infer the network topology from experimental data, less emphasis has been placed on methods that infer network dynamics. Furthermore, since the network inference problem is typically underdetermined, it is essential to have the option of incorporating into the inference process, prior knowledge about the network, along with an effective description of the search space of dynamic models. Finally, it is also important to have an understanding of how a given inference method is affected by experimental and other noise in the data used. This paper contains a novel inference algorithm using the algebraic framework of Boolean polynomial dynamical systems (BPDS), meeting all these requirements. The algorithm takes as input time series data, including those from network perturbations, such as knock-out mutant strains and RNAi experiments. It allows for the incorporation of prior biological knowledge while being robust to significant levels of noise in the data used for inference. It uses an evolutionary algorithm for local optimization with an encoding of the mathematical models as BPDS. The BPDS framework allows an effective representation of the search space for algebraic dynamic models that improves computational performance. The algorithm is validated with both simulated and experimental microarray expression profile data. Robustness to noise is tested using a published mathematical model of the segment polarity gene network in Drosophila melanogaster. Benchmarking of the algorithm is done by comparison with a spectrum of state-of-the-art network inference methods on data from the synthetic IRMA network to demonstrate that our method has good precision and recall for the network reconstruction task, while also predicting several of the dynamic patterns present in the network. Boolean polynomial dynamical systems provide a powerful modeling framework for the reverse engineering of gene regulatory networks, that enables a rich mathematical structure on the model search space. A C++ implementation of the method, distributed under LPGL license, is available, together with the source code, at http://www.paola-vera-licona.net/Software/EARevEng/REACT.html.
Network inference using informative priors

PubMed Central

Mukherjee, Sach; Speed, Terence P.

2008-01-01

Recent years have seen much interest in the study of systems characterized by multiple interacting components. A class of statistical models called graphical models, in which graphs are used to represent probabilistic relationships between variables, provides a framework for formal inference regarding such systems. In many settings, the object of inference is the network structure itself. This problem of “network inference” is well known to be a challenging one. However, in scientific settings there is very often existing information regarding network connectivity. A natural idea then is to take account of such information during inference. This article addresses the question of incorporating prior information into network inference. We focus on directed models called Bayesian networks, and use Markov chain Monte Carlo to draw samples from posterior distributions over network structures. We introduce prior distributions on graphs capable of capturing information regarding network features including edges, classes of edges, degree distributions, and sparsity. We illustrate our approach in the context of systems biology, applying our methods to network inference in cancer signaling. PMID:18799736
A Hierarchical Poisson Log-Normal Model for Network Inference from RNA Sequencing Data

PubMed Central

Gallopin, Mélina; Rau, Andrea; Jaffrézic, Florence

2013-01-01

Gene network inference from transcriptomic data is an important methodological challenge and a key aspect of systems biology. Although several methods have been proposed to infer networks from microarray data, there is a need for inference methods able to model RNA-seq data, which are count-based and highly variable. In this work we propose a hierarchical Poisson log-normal model with a Lasso penalty to infer gene networks from RNA-seq data; this model has the advantage of directly modelling discrete data and accounting for inter-sample variance larger than the sample mean. Using real microRNA-seq data from breast cancer tumors and simulations, we compare this method to a regularized Gaussian graphical model on log-transformed data, and a Poisson log-linear graphical model with a Lasso penalty on power-transformed data. For data simulated with large inter-sample dispersion, the proposed model performs better than the other methods in terms of sensitivity, specificity and area under the ROC curve. These results show the necessity of methods specifically designed for gene network inference from RNA-seq data. PMID:24147011
An algebra-based method for inferring gene regulatory networks

PubMed Central

2014-01-01

Background The inference of gene regulatory networks (GRNs) from experimental observations is at the heart of systems biology. This includes the inference of both the network topology and its dynamics. While there are many algorithms available to infer the network topology from experimental data, less emphasis has been placed on methods that infer network dynamics. Furthermore, since the network inference problem is typically underdetermined, it is essential to have the option of incorporating into the inference process, prior knowledge about the network, along with an effective description of the search space of dynamic models. Finally, it is also important to have an understanding of how a given inference method is affected by experimental and other noise in the data used. Results This paper contains a novel inference algorithm using the algebraic framework of Boolean polynomial dynamical systems (BPDS), meeting all these requirements. The algorithm takes as input time series data, including those from network perturbations, such as knock-out mutant strains and RNAi experiments. It allows for the incorporation of prior biological knowledge while being robust to significant levels of noise in the data used for inference. It uses an evolutionary algorithm for local optimization with an encoding of the mathematical models as BPDS. The BPDS framework allows an effective representation of the search space for algebraic dynamic models that improves computational performance. The algorithm is validated with both simulated and experimental microarray expression profile data. Robustness to noise is tested using a published mathematical model of the segment polarity gene network in Drosophila melanogaster. Benchmarking of the algorithm is done by comparison with a spectrum of state-of-the-art network inference methods on data from the synthetic IRMA network to demonstrate that our method has good precision and recall for the network reconstruction task, while also predicting several of the dynamic patterns present in the network. Conclusions Boolean polynomial dynamical systems provide a powerful modeling framework for the reverse engineering of gene regulatory networks, that enables a rich mathematical structure on the model search space. A C++ implementation of the method, distributed under LPGL license, is available, together with the source code, at http://www.paola-vera-licona.net/Software/EARevEng/REACT.html. PMID:24669835
Inference of scale-free networks from gene expression time series.

PubMed

Daisuke, Tominaga; Horton, Paul

2006-04-01

Quantitative time-series observation of gene expression is becoming possible, for example by cell array technology. However, there are no practical methods with which to infer network structures using only observed time-series data. As most computational models of biological networks for continuous time-series data have a high degree of freedom, it is almost impossible to infer the correct structures. On the other hand, it has been reported that some kinds of biological networks, such as gene networks and metabolic pathways, may have scale-free properties. We hypothesize that the architecture of inferred biological network models can be restricted to scale-free networks. We developed an inference algorithm for biological networks using only time-series data by introducing such a restriction. We adopt the S-system as the network model, and a distributed genetic algorithm to optimize models to fit its simulated results to observed time series data. We have tested our algorithm on a case study (simulated data). We compared optimization under no restriction, which allows for a fully connected network, and under the restriction that the total number of links must equal that expected from a scale free network. The restriction reduced both false positive and false negative estimation of the links and also the differences between model simulation and the given time-series data.
Automatic inference of multicellular regulatory networks using informative priors.

PubMed

Sun, Xiaoyun; Hong, Pengyu

2009-01-01

To fully understand the mechanisms governing animal development, computational models and algorithms are needed to enable quantitative studies of the underlying regulatory networks. We developed a mathematical model based on dynamic Bayesian networks to model multicellular regulatory networks that govern cell differentiation processes. A machine-learning method was developed to automatically infer such a model from heterogeneous data. We show that the model inference procedure can be greatly improved by incorporating interaction data across species. The proposed approach was applied to C. elegans vulval induction to reconstruct a model capable of simulating C. elegans vulval induction under 73 different genetic conditions.
State Space Model with hidden variables for reconstruction of gene regulatory networks.

PubMed

Wu, Xi; Li, Peng; Wang, Nan; Gong, Ping; Perkins, Edward J; Deng, Youping; Zhang, Chaoyang

2011-01-01

State Space Model (SSM) is a relatively new approach to inferring gene regulatory networks. It requires less computational time than Dynamic Bayesian Networks (DBN). There are two types of variables in the linear SSM, observed variables and hidden variables. SSM uses an iterative method, namely Expectation-Maximization, to infer regulatory relationships from microarray datasets. The hidden variables cannot be directly observed from experiments. How to determine the number of hidden variables has a significant impact on the accuracy of network inference. In this study, we used SSM to infer Gene regulatory networks (GRNs) from synthetic time series datasets, investigated Bayesian Information Criterion (BIC) and Principle Component Analysis (PCA) approaches to determining the number of hidden variables in SSM, and evaluated the performance of SSM in comparison with DBN. True GRNs and synthetic gene expression datasets were generated using GeneNetWeaver. Both DBN and linear SSM were used to infer GRNs from the synthetic datasets. The inferred networks were compared with the true networks. Our results show that inference precision varied with the number of hidden variables. For some regulatory networks, the inference precision of DBN was higher but SSM performed better in other cases. Although the overall performance of the two approaches is compatible, SSM is much faster and capable of inferring much larger networks than DBN. This study provides useful information in handling the hidden variables and improving the inference precision.
Functional Inference of Complex Anatomical Tendinous Networks at a Macroscopic Scale via Sparse Experimentation

PubMed Central

Saxena, Anupam; Lipson, Hod; Valero-Cuevas, Francisco J.

2012-01-01

In systems and computational biology, much effort is devoted to functional identification of systems and networks at the molecular-or cellular scale. However, similarly important networks exist at anatomical scales such as the tendon network of human fingers: the complex array of collagen fibers that transmits and distributes muscle forces to finger joints. This network is critical to the versatility of the human hand, and its function has been debated since at least the 16th century. Here, we experimentally infer the structure (both topology and parameter values) of this network through sparse interrogation with force inputs. A population of models representing this structure co-evolves in simulation with a population of informative future force inputs via the predator-prey estimation-exploration algorithm. Model fitness depends on their ability to explain experimental data, while the fitness of future force inputs depends on causing maximal functional discrepancy among current models. We validate our approach by inferring two known synthetic Latex networks, and one anatomical tendon network harvested from a cadaver's middle finger. We find that functionally similar but structurally diverse models can exist within a narrow range of the training set and cross-validation errors. For the Latex networks, models with low training set error [<4%] and resembling the known network have the smallest cross-validation errors [∼5%]. The low training set [<4%] and cross validation [<7.2%] errors for models for the cadaveric specimen demonstrate what, to our knowledge, is the first experimental inference of the functional structure of complex anatomical networks. This work expands current bioinformatics inference approaches by demonstrating that sparse, yet informative interrogation of biological specimens holds significant computational advantages in accurate and efficient inference over random testing, or assuming model topology and only inferring parameters values. These findings also hold clues to both our evolutionary history and the development of versatile machines. PMID:23144601
Functional inference of complex anatomical tendinous networks at a macroscopic scale via sparse experimentation.

PubMed

Saxena, Anupam; Lipson, Hod; Valero-Cuevas, Francisco J

2012-01-01

In systems and computational biology, much effort is devoted to functional identification of systems and networks at the molecular-or cellular scale. However, similarly important networks exist at anatomical scales such as the tendon network of human fingers: the complex array of collagen fibers that transmits and distributes muscle forces to finger joints. This network is critical to the versatility of the human hand, and its function has been debated since at least the 16(th) century. Here, we experimentally infer the structure (both topology and parameter values) of this network through sparse interrogation with force inputs. A population of models representing this structure co-evolves in simulation with a population of informative future force inputs via the predator-prey estimation-exploration algorithm. Model fitness depends on their ability to explain experimental data, while the fitness of future force inputs depends on causing maximal functional discrepancy among current models. We validate our approach by inferring two known synthetic Latex networks, and one anatomical tendon network harvested from a cadaver's middle finger. We find that functionally similar but structurally diverse models can exist within a narrow range of the training set and cross-validation errors. For the Latex networks, models with low training set error [<4%] and resembling the known network have the smallest cross-validation errors [∼5%]. The low training set [<4%] and cross validation [<7.2%] errors for models for the cadaveric specimen demonstrate what, to our knowledge, is the first experimental inference of the functional structure of complex anatomical networks. This work expands current bioinformatics inference approaches by demonstrating that sparse, yet informative interrogation of biological specimens holds significant computational advantages in accurate and efficient inference over random testing, or assuming model topology and only inferring parameters values. These findings also hold clues to both our evolutionary history and the development of versatile machines.
Inference of Vohradský's Models of Genetic Networks by Solving Two-Dimensional Function Optimization Problems

PubMed Central

Kimura, Shuhei; Sato, Masanao; Okada-Hatakeyama, Mariko

2013-01-01

The inference of a genetic network is a problem in which mutual interactions among genes are inferred from time-series of gene expression levels. While a number of models have been proposed to describe genetic networks, this study focuses on a mathematical model proposed by Vohradský. Because of its advantageous features, several researchers have proposed the inference methods based on Vohradský's model. When trying to analyze large-scale networks consisting of dozens of genes, however, these methods must solve high-dimensional non-linear function optimization problems. In order to resolve the difficulty of estimating the parameters of the Vohradský's model, this study proposes a new method that defines the problem as several two-dimensional function optimization problems. Through numerical experiments on artificial genetic network inference problems, we showed that, although the computation time of the proposed method is not the shortest, the method has the ability to estimate parameters of Vohradský's models more effectively with sufficiently short computation times. This study then applied the proposed method to an actual inference problem of the bacterial SOS DNA repair system, and succeeded in finding several reasonable regulations. PMID:24386175
Functional networks inference from rule-based machine learning models.

PubMed

Lazzarini, Nicola; Widera, Paweł; Williamson, Stuart; Heer, Rakesh; Krasnogor, Natalio; Bacardit, Jaume

2016-01-01

Functional networks play an important role in the analysis of biological processes and systems. The inference of these networks from high-throughput (-omics) data is an area of intense research. So far, the similarity-based inference paradigm (e.g. gene co-expression) has been the most popular approach. It assumes a functional relationship between genes which are expressed at similar levels across different samples. An alternative to this paradigm is the inference of relationships from the structure of machine learning models. These models are able to capture complex relationships between variables, that often are different/complementary to the similarity-based methods. We propose a protocol to infer functional networks from machine learning models, called FuNeL. It assumes, that genes used together within a rule-based machine learning model to classify the samples, might also be functionally related at a biological level. The protocol is first tested on synthetic datasets and then evaluated on a test suite of 8 real-world datasets related to human cancer. The networks inferred from the real-world data are compared against gene co-expression networks of equal size, generated with 3 different methods. The comparison is performed from two different points of view. We analyse the enriched biological terms in the set of network nodes and the relationships between known disease-associated genes in a context of the network topology. The comparison confirms both the biological relevance and the complementary character of the knowledge captured by the FuNeL networks in relation to similarity-based methods and demonstrates its potential to identify known disease associations as core elements of the network. Finally, using a prostate cancer dataset as a case study, we confirm that the biological knowledge captured by our method is relevant to the disease and consistent with the specialised literature and with an independent dataset not used in the inference process. The implementation of our network inference protocol is available at: http://ico2s.org/software/funel.html.
Bayesian Inference and Online Learning in Poisson Neuronal Networks.

PubMed

Huang, Yanping; Rao, Rajesh P N

2016-08-01

Motivated by the growing evidence for Bayesian computation in the brain, we show how a two-layer recurrent network of Poisson neurons can perform both approximate Bayesian inference and learning for any hidden Markov model. The lower-layer sensory neurons receive noisy measurements of hidden world states. The higher-layer neurons infer a posterior distribution over world states via Bayesian inference from inputs generated by sensory neurons. We demonstrate how such a neuronal network with synaptic plasticity can implement a form of Bayesian inference similar to Monte Carlo methods such as particle filtering. Each spike in a higher-layer neuron represents a sample of a particular hidden world state. The spiking activity across the neural population approximates the posterior distribution over hidden states. In this model, variability in spiking is regarded not as a nuisance but as an integral feature that provides the variability necessary for sampling during inference. We demonstrate how the network can learn the likelihood model, as well as the transition probabilities underlying the dynamics, using a Hebbian learning rule. We present results illustrating the ability of the network to perform inference and learning for arbitrary hidden Markov models.
A prior-based integrative framework for functional transcriptional regulatory network inference

PubMed Central

Siahpirani, Alireza F.

2017-01-01

Abstract Transcriptional regulatory networks specify regulatory proteins controlling the context-specific expression levels of genes. Inference of genome-wide regulatory networks is central to understanding gene regulation, but remains an open challenge. Expression-based network inference is among the most popular methods to infer regulatory networks, however, networks inferred from such methods have low overlap with experimentally derived (e.g. ChIP-chip and transcription factor (TF) knockouts) networks. Currently we have a limited understanding of this discrepancy. To address this gap, we first develop a regulatory network inference algorithm, based on probabilistic graphical models, to integrate expression with auxiliary datasets supporting a regulatory edge. Second, we comprehensively analyze our and other state-of-the-art methods on different expression perturbation datasets. Networks inferred by integrating sequence-specific motifs with expression have substantially greater agreement with experimentally derived networks, while remaining more predictive of expression than motif-based networks. Our analysis suggests natural genetic variation as the most informative perturbation for network inference, and, identifies core TFs whose targets are predictable from expression. Multiple reasons make the identification of targets of other TFs difficult, including network architecture and insufficient variation of TF mRNA level. Finally, we demonstrate the utility of our inference algorithm to infer stress-specific regulatory networks and for regulator prioritization. PMID:27794550
Gene network inference by fusing data from diverse distributions

PubMed Central

Žitnik, Marinka; Zupan, Blaž

2015-01-01

Motivation: Markov networks are undirected graphical models that are widely used to infer relations between genes from experimental data. Their state-of-the-art inference procedures assume the data arise from a Gaussian distribution. High-throughput omics data, such as that from next generation sequencing, often violates this assumption. Furthermore, when collected data arise from multiple related but otherwise nonidentical distributions, their underlying networks are likely to have common features. New principled statistical approaches are needed that can deal with different data distributions and jointly consider collections of datasets. Results: We present FuseNet, a Markov network formulation that infers networks from a collection of nonidentically distributed datasets. Our approach is computationally efficient and general: given any number of distributions from an exponential family, FuseNet represents model parameters through shared latent factors that define neighborhoods of network nodes. In a simulation study, we demonstrate good predictive performance of FuseNet in comparison to several popular graphical models. We show its effectiveness in an application to breast cancer RNA-sequencing and somatic mutation data, a novel application of graphical models. Fusion of datasets offers substantial gains relative to inference of separate networks for each dataset. Our results demonstrate that network inference methods for non-Gaussian data can help in accurate modeling of the data generated by emergent high-throughput technologies. Availability and implementation: Source code is at https://github.com/marinkaz/fusenet. Contact: blaz.zupan@fri.uni-lj.si Supplementary information: Supplementary information is available at Bioinformatics online. PMID:26072487
Genetic network inference as a series of discrimination tasks.

PubMed

Kimura, Shuhei; Nakayama, Satoshi; Hatakeyama, Mariko

2009-04-01

Genetic network inference methods based on sets of differential equations generally require a great deal of time, as the equations must be solved many times. To reduce the computational cost, researchers have proposed other methods for inferring genetic networks by solving sets of differential equations only a few times, or even without solving them at all. When we try to obtain reasonable network models using these methods, however, we must estimate the time derivatives of the gene expression levels with great precision. In this study, we propose a new method to overcome the drawbacks of inference methods based on sets of differential equations. Our method infers genetic networks by obtaining classifiers capable of predicting the signs of the derivatives of the gene expression levels. For this purpose, we defined a genetic network inference problem as a series of discrimination tasks, then solved the defined series of discrimination tasks with a linear programming machine. Our experimental results demonstrated that the proposed method is capable of correctly inferring genetic networks, and doing so more than 500 times faster than the other inference methods based on sets of differential equations. Next, we applied our method to actual expression data of the bacterial SOS DNA repair system. And finally, we demonstrated that our approach relates to the inference method based on the S-system model. Though our method provides no estimation of the kinetic parameters, it should be useful for researchers interested only in the network structure of a target system. Supplementary data are available at Bioinformatics online.
Probabilistic Inference in General Graphical Models through Sampling in Stochastic Networks of Spiking Neurons

PubMed Central

Pecevski, Dejan; Buesing, Lars; Maass, Wolfgang

2011-01-01

An important open problem of computational neuroscience is the generic organization of computations in networks of neurons in the brain. We show here through rigorous theoretical analysis that inherent stochastic features of spiking neurons, in combination with simple nonlinear computational operations in specific network motifs and dendritic arbors, enable networks of spiking neurons to carry out probabilistic inference through sampling in general graphical models. In particular, it enables them to carry out probabilistic inference in Bayesian networks with converging arrows (“explaining away”) and with undirected loops, that occur in many real-world tasks. Ubiquitous stochastic features of networks of spiking neurons, such as trial-to-trial variability and spontaneous activity, are necessary ingredients of the underlying computational organization. We demonstrate through computer simulations that this approach can be scaled up to neural emulations of probabilistic inference in fairly large graphical models, yielding some of the most complex computations that have been carried out so far in networks of spiking neurons. PMID:22219717
Designing a parallel evolutionary algorithm for inferring gene networks on the cloud computing environment.

PubMed

Lee, Wei-Po; Hsiao, Yu-Ting; Hwang, Wei-Che

2014-01-16

To improve the tedious task of reconstructing gene networks through testing experimentally the possible interactions between genes, it becomes a trend to adopt the automated reverse engineering procedure instead. Some evolutionary algorithms have been suggested for deriving network parameters. However, to infer large networks by the evolutionary algorithm, it is necessary to address two important issues: premature convergence and high computational cost. To tackle the former problem and to enhance the performance of traditional evolutionary algorithms, it is advisable to use parallel model evolutionary algorithms. To overcome the latter and to speed up the computation, it is advocated to adopt the mechanism of cloud computing as a promising solution: most popular is the method of MapReduce programming model, a fault-tolerant framework to implement parallel algorithms for inferring large gene networks. This work presents a practical framework to infer large gene networks, by developing and parallelizing a hybrid GA-PSO optimization method. Our parallel method is extended to work with the Hadoop MapReduce programming model and is executed in different cloud computing environments. To evaluate the proposed approach, we use a well-known open-source software GeneNetWeaver to create several yeast S. cerevisiae sub-networks and use them to produce gene profiles. Experiments have been conducted and the results have been analyzed. They show that our parallel approach can be successfully used to infer networks with desired behaviors and the computation time can be largely reduced. Parallel population-based algorithms can effectively determine network parameters and they perform better than the widely-used sequential algorithms in gene network inference. These parallel algorithms can be distributed to the cloud computing environment to speed up the computation. By coupling the parallel model population-based optimization method and the parallel computational framework, high quality solutions can be obtained within relatively short time. This integrated approach is a promising way for inferring large networks.
Designing a parallel evolutionary algorithm for inferring gene networks on the cloud computing environment

PubMed Central

2014-01-01

Background To improve the tedious task of reconstructing gene networks through testing experimentally the possible interactions between genes, it becomes a trend to adopt the automated reverse engineering procedure instead. Some evolutionary algorithms have been suggested for deriving network parameters. However, to infer large networks by the evolutionary algorithm, it is necessary to address two important issues: premature convergence and high computational cost. To tackle the former problem and to enhance the performance of traditional evolutionary algorithms, it is advisable to use parallel model evolutionary algorithms. To overcome the latter and to speed up the computation, it is advocated to adopt the mechanism of cloud computing as a promising solution: most popular is the method of MapReduce programming model, a fault-tolerant framework to implement parallel algorithms for inferring large gene networks. Results This work presents a practical framework to infer large gene networks, by developing and parallelizing a hybrid GA-PSO optimization method. Our parallel method is extended to work with the Hadoop MapReduce programming model and is executed in different cloud computing environments. To evaluate the proposed approach, we use a well-known open-source software GeneNetWeaver to create several yeast S. cerevisiae sub-networks and use them to produce gene profiles. Experiments have been conducted and the results have been analyzed. They show that our parallel approach can be successfully used to infer networks with desired behaviors and the computation time can be largely reduced. Conclusions Parallel population-based algorithms can effectively determine network parameters and they perform better than the widely-used sequential algorithms in gene network inference. These parallel algorithms can be distributed to the cloud computing environment to speed up the computation. By coupling the parallel model population-based optimization method and the parallel computational framework, high quality solutions can be obtained within relatively short time. This integrated approach is a promising way for inferring large networks. PMID:24428926

Inferring Gene Regulatory Networks by Singular Value Decomposition and Gravitation Field Algorithm

PubMed Central

Zheng, Ming; Wu, Jia-nan; Huang, Yan-xin; Liu, Gui-xia; Zhou, You; Zhou, Chun-guang

2012-01-01

Reconstruction of gene regulatory networks (GRNs) is of utmost interest and has become a challenge computational problem in system biology. However, every existing inference algorithm from gene expression profiles has its own advantages and disadvantages. In particular, the effectiveness and efficiency of every previous algorithm is not high enough. In this work, we proposed a novel inference algorithm from gene expression data based on differential equation model. In this algorithm, two methods were included for inferring GRNs. Before reconstructing GRNs, singular value decomposition method was used to decompose gene expression data, determine the algorithm solution space, and get all candidate solutions of GRNs. In these generated family of candidate solutions, gravitation field algorithm was modified to infer GRNs, used to optimize the criteria of differential equation model, and search the best network structure result. The proposed algorithm is validated on both the simulated scale-free network and real benchmark gene regulatory network in networks database. Both the Bayesian method and the traditional differential equation model were also used to infer GRNs, and the results were used to compare with the proposed algorithm in our work. And genetic algorithm and simulated annealing were also used to evaluate gravitation field algorithm. The cross-validation results confirmed the effectiveness of our algorithm, which outperforms significantly other previous algorithms. PMID:23226565
Explaining Inference on a Population of Independent Agents Using Bayesian Networks

ERIC Educational Resources Information Center

Sutovsky, Peter

2013-01-01

The main goal of this research is to design, implement, and evaluate a novel explanation method, the hierarchical explanation method (HEM), for explaining Bayesian network (BN) inference when the network is modeling a population of conditionally independent agents, each of which is modeled as a subnetwork. For example, consider disease-outbreak…
Inferring Plasmodium vivax Transmission Networks from Tempo-Spatial Surveillance Data

PubMed Central

Shi, Benyun; Liu, Jiming; Zhou, Xiao-Nong; Yang, Guo-Jing

2014-01-01

Background The transmission networks of Plasmodium vivax characterize how the parasite transmits from one location to another, which are informative and insightful for public health policy makers to accurately predict the patterns of its geographical spread. However, such networks are not apparent from surveillance data because P. vivax transmission can be affected by many factors, such as the biological characteristics of mosquitoes and the mobility of human beings. Here, we pay special attention to the problem of how to infer the underlying transmission networks of P. vivax based on available tempo-spatial patterns of reported cases. Methodology We first define a spatial transmission model, which involves representing both the heterogeneous transmission potential of P. vivax at individual locations and the mobility of infected populations among different locations. Based on the proposed transmission model, we further introduce a recurrent neural network model to infer the transmission networks from surveillance data. Specifically, in this model, we take into account multiple real-world factors, including the length of P. vivax incubation period, the impact of malaria control at different locations, and the total number of imported cases. Principal Findings We implement our proposed models by focusing on the P. vivax transmission among 62 towns in Yunnan province, People's Republic China, which have been experiencing high malaria transmission in the past years. By conducting scenario analysis with respect to different numbers of imported cases, we can (i) infer the underlying P. vivax transmission networks, (ii) estimate the number of imported cases for each individual town, and (iii) quantify the roles of individual towns in the geographical spread of P. vivax. Conclusion The demonstrated models have presented a general means for inferring the underlying transmission networks from surveillance data. The inferred networks will offer new insights into how to improve the predictability of P. vivax transmission. PMID:24516684
Comparative evaluation of reverse engineering gene regulatory networks with relevance networks, graphical gaussian models and bayesian networks.

PubMed

Werhli, Adriano V; Grzegorczyk, Marco; Husmeier, Dirk

2006-10-15

An important problem in systems biology is the inference of biochemical pathways and regulatory networks from postgenomic data. Various reverse engineering methods have been proposed in the literature, and it is important to understand their relative merits and shortcomings. In the present paper, we compare the accuracy of reconstructing gene regulatory networks with three different modelling and inference paradigms: (1) Relevance networks (RNs): pairwise association scores independent of the remaining network; (2) graphical Gaussian models (GGMs): undirected graphical models with constraint-based inference, and (3) Bayesian networks (BNs): directed graphical models with score-based inference. The evaluation is carried out on the Raf pathway, a cellular signalling network describing the interaction of 11 phosphorylated proteins and phospholipids in human immune system cells. We use both laboratory data from cytometry experiments as well as data simulated from the gold-standard network. We also compare passive observations with active interventions. On Gaussian observational data, BNs and GGMs were found to outperform RNs. The difference in performance was not significant for the non-linear simulated data and the cytoflow data, though. Also, we did not observe a significant difference between BNs and GGMs on observational data in general. However, for interventional data, BNs outperform GGMs and RNs, especially when taking the edge directions rather than just the skeletons of the graphs into account. This suggests that the higher computational costs of inference with BNs over GGMs and RNs are not justified when using only passive observations, but that active interventions in the form of gene knockouts and over-expressions are required to exploit the full potential of BNs. Data, software and supplementary material are available from http://www.bioss.sari.ac.uk/staff/adriano/research.html
Inference of neuronal network spike dynamics and topology from calcium imaging data

PubMed Central

Lütcke, Henry; Gerhard, Felipe; Zenke, Friedemann; Gerstner, Wulfram; Helmchen, Fritjof

2013-01-01

Two-photon calcium imaging enables functional analysis of neuronal circuits by inferring action potential (AP) occurrence (“spike trains”) from cellular fluorescence signals. It remains unclear how experimental parameters such as signal-to-noise ratio (SNR) and acquisition rate affect spike inference and whether additional information about network structure can be extracted. Here we present a simulation framework for quantitatively assessing how well spike dynamics and network topology can be inferred from noisy calcium imaging data. For simulated AP-evoked calcium transients in neocortical pyramidal cells, we analyzed the quality of spike inference as a function of SNR and data acquisition rate using a recently introduced peeling algorithm. Given experimentally attainable values of SNR and acquisition rate, neural spike trains could be reconstructed accurately and with up to millisecond precision. We then applied statistical neuronal network models to explore how remaining uncertainties in spike inference affect estimates of network connectivity and topological features of network organization. We define the experimental conditions suitable for inferring whether the network has a scale-free structure and determine how well hub neurons can be identified. Our findings provide a benchmark for future calcium imaging studies that aim to reliably infer neuronal network properties. PMID:24399936
Boolean Networks in Inference and Dynamic Modeling of Biological Systems at the Molecular and Physiological Level

NASA Astrophysics Data System (ADS)

Thakar, Juilee; Albert, Réka

The following sections are included: * Introduction * Boolean Network Concepts and History * Extensions of the Classical Boolean Framework * Boolean Inference Methods and Examples in Biology * Dynamic Boolean Models: Examples in Plant Biology, Developmental Biology and Immunology * Conclusions * References
Social networks help to infer causality in the tumor microenvironment.

PubMed

Crespo, Isaac; Doucey, Marie-Agnès; Xenarios, Ioannis

2016-03-15

Networks have become a popular way to conceptualize a system of interacting elements, such as electronic circuits, social communication, metabolism or gene regulation. Network inference, analysis, and modeling techniques have been developed in different areas of science and technology, such as computer science, mathematics, physics, and biology, with an active interdisciplinary exchange of concepts and approaches. However, some concepts seem to belong to a specific field without a clear transferability to other domains. At the same time, it is increasingly recognized that within some biological systems--such as the tumor microenvironment--where different types of resident and infiltrating cells interact to carry out their functions, the complexity of the system demands a theoretical framework, such as statistical inference, graph analysis and dynamical models, in order to asses and study the information derived from high-throughput experimental technologies. In this article we propose to adopt and adapt the concepts of influence and investment from the world of social network analysis to biological problems, and in particular to apply this approach to infer causality in the tumor microenvironment. We showed that constructing a bidirectional network of influence between cell and cell communication molecules allowed us to determine the direction of inferred regulations at the expression level and correctly recapitulate cause-effect relationships described in literature. This work constitutes an example of a transfer of knowledge and concepts from the world of social network analysis to biomedical research, in particular to infer network causality in biological networks. This causality elucidation is essential to model the homeostatic response of biological systems to internal and external factors, such as environmental conditions, pathogens or treatments.
Nonparametric Bayesian inference of the microcanonical stochastic block model

NASA Astrophysics Data System (ADS)

Peixoto, Tiago P.

2017-01-01

A principled approach to characterize the hidden modular structure of networks is to formulate generative models and then infer their parameters from data. When the desired structure is composed of modules or "communities," a suitable choice for this task is the stochastic block model (SBM), where nodes are divided into groups, and the placement of edges is conditioned on the group memberships. Here, we present a nonparametric Bayesian method to infer the modular structure of empirical networks, including the number of modules and their hierarchical organization. We focus on a microcanonical variant of the SBM, where the structure is imposed via hard constraints, i.e., the generated networks are not allowed to violate the patterns imposed by the model. We show how this simple model variation allows simultaneously for two important improvements over more traditional inference approaches: (1) deeper Bayesian hierarchies, with noninformative priors replaced by sequences of priors and hyperpriors, which not only remove limitations that seriously degrade the inference on large networks but also reveal structures at multiple scales; (2) a very efficient inference algorithm that scales well not only for networks with a large number of nodes and edges but also with an unlimited number of modules. We show also how this approach can be used to sample modular hierarchies from the posterior distribution, as well as to perform model selection. We discuss and analyze the differences between sampling from the posterior and simply finding the single parameter estimate that maximizes it. Furthermore, we expose a direct equivalence between our microcanonical approach and alternative derivations based on the canonical SBM.
The Role of Probability-Based Inference in an Intelligent Tutoring System.

ERIC Educational Resources Information Center

Mislevy, Robert J.; Gitomer, Drew H.

Probability-based inference in complex networks of interdependent variables is an active topic in statistical research, spurred by such diverse applications as forecasting, pedigree analysis, troubleshooting, and medical diagnosis. This paper concerns the role of Bayesian inference networks for updating student models in intelligent tutoring…
Inference of gene regulatory networks from time series by Tsallis entropy

PubMed Central

2011-01-01

Background The inference of gene regulatory networks (GRNs) from large-scale expression profiles is one of the most challenging problems of Systems Biology nowadays. Many techniques and models have been proposed for this task. However, it is not generally possible to recover the original topology with great accuracy, mainly due to the short time series data in face of the high complexity of the networks and the intrinsic noise of the expression measurements. In order to improve the accuracy of GRNs inference methods based on entropy (mutual information), a new criterion function is here proposed. Results In this paper we introduce the use of generalized entropy proposed by Tsallis, for the inference of GRNs from time series expression profiles. The inference process is based on a feature selection approach and the conditional entropy is applied as criterion function. In order to assess the proposed methodology, the algorithm is applied to recover the network topology from temporal expressions generated by an artificial gene network (AGN) model as well as from the DREAM challenge. The adopted AGN is based on theoretical models of complex networks and its gene transference function is obtained from random drawing on the set of possible Boolean functions, thus creating its dynamics. On the other hand, DREAM time series data presents variation of network size and its topologies are based on real networks. The dynamics are generated by continuous differential equations with noise and perturbation. By adopting both data sources, it is possible to estimate the average quality of the inference with respect to different network topologies, transfer functions and network sizes. Conclusions A remarkable improvement of accuracy was observed in the experimental results by reducing the number of false connections in the inferred topology by the non-Shannon entropy. The obtained best free parameter of the Tsallis entropy was on average in the range 2.5 ≤ q ≤ 3.5 (hence, subextensive entropy), which opens new perspectives for GRNs inference methods based on information theory and for investigation of the nonextensivity of such networks. The inference algorithm and criterion function proposed here were implemented and included in the DimReduction software, which is freely available at http://sourceforge.net/projects/dimreduction and http://code.google.com/p/dimreduction/. PMID:21545720
Inferring causal molecular networks: empirical assessment through a community-based effort

PubMed Central

Hill, Steven M.; Heiser, Laura M.; Cokelaer, Thomas; Unger, Michael; Nesser, Nicole K.; Carlin, Daniel E.; Zhang, Yang; Sokolov, Artem; Paull, Evan O.; Wong, Chris K.; Graim, Kiley; Bivol, Adrian; Wang, Haizhou; Zhu, Fan; Afsari, Bahman; Danilova, Ludmila V.; Favorov, Alexander V.; Lee, Wai Shing; Taylor, Dane; Hu, Chenyue W.; Long, Byron L.; Noren, David P.; Bisberg, Alexander J.; Mills, Gordon B.; Gray, Joe W.; Kellen, Michael; Norman, Thea; Friend, Stephen; Qutub, Amina A.; Fertig, Elana J.; Guan, Yuanfang; Song, Mingzhou; Stuart, Joshua M.; Spellman, Paul T.; Koeppl, Heinz; Stolovitzky, Gustavo; Saez-Rodriguez, Julio; Mukherjee, Sach

2016-01-01

Inferring molecular networks is a central challenge in computational biology. However, it has remained unclear whether causal, rather than merely correlational, relationships can be effectively inferred in complex biological settings. Here we describe the HPN-DREAM network inference challenge that focused on learning causal influences in signaling networks. We used phosphoprotein data from cancer cell lines as well as in silico data from a nonlinear dynamical model. Using the phosphoprotein data, we scored more than 2,000 networks submitted by challenge participants. The networks spanned 32 biological contexts and were scored in terms of causal validity with respect to unseen interventional data. A number of approaches were effective and incorporating known biology was generally advantageous. Additional sub-challenges considered time-course prediction and visualization. Our results constitute the most comprehensive assessment of causal network inference in a mammalian setting carried out to date and suggest that learning causal relationships may be feasible in complex settings such as disease states. Furthermore, our scoring approach provides a practical way to empirically assess the causal validity of inferred molecular networks. PMID:26901648
Network Model-Assisted Inference from Respondent-Driven Sampling Data

PubMed Central

Gile, Krista J.; Handcock, Mark S.

2015-01-01

Summary Respondent-Driven Sampling is a widely-used method for sampling hard-to-reach human populations by link-tracing over their social networks. Inference from such data requires specialized techniques because the sampling process is both partially beyond the control of the researcher, and partially implicitly defined. Therefore, it is not generally possible to directly compute the sampling weights for traditional design-based inference, and likelihood inference requires modeling the complex sampling process. As an alternative, we introduce a model-assisted approach, resulting in a design-based estimator leveraging a working network model. We derive a new class of estimators for population means and a corresponding bootstrap standard error estimator. We demonstrate improved performance compared to existing estimators, including adjustment for an initial convenience sample. We also apply the method and an extension to the estimation of HIV prevalence in a high-risk population. PMID:26640328
Network Model-Assisted Inference from Respondent-Driven Sampling Data.

PubMed

Gile, Krista J; Handcock, Mark S

2015-06-01

Respondent-Driven Sampling is a widely-used method for sampling hard-to-reach human populations by link-tracing over their social networks. Inference from such data requires specialized techniques because the sampling process is both partially beyond the control of the researcher, and partially implicitly defined. Therefore, it is not generally possible to directly compute the sampling weights for traditional design-based inference, and likelihood inference requires modeling the complex sampling process. As an alternative, we introduce a model-assisted approach, resulting in a design-based estimator leveraging a working network model. We derive a new class of estimators for population means and a corresponding bootstrap standard error estimator. We demonstrate improved performance compared to existing estimators, including adjustment for an initial convenience sample. We also apply the method and an extension to the estimation of HIV prevalence in a high-risk population.
Hybrid regulatory models: a statistically tractable approach to model regulatory network dynamics.

PubMed

Ocone, Andrea; Millar, Andrew J; Sanguinetti, Guido

2013-04-01

Computational modelling of the dynamics of gene regulatory networks is a central task of systems biology. For networks of small/medium scale, the dominant paradigm is represented by systems of coupled non-linear ordinary differential equations (ODEs). ODEs afford great mechanistic detail and flexibility, but calibrating these models to data is often an extremely difficult statistical problem. Here, we develop a general statistical inference framework for stochastic transcription-translation networks. We use a coarse-grained approach, which represents the system as a network of stochastic (binary) promoter and (continuous) protein variables. We derive an exact inference algorithm and an efficient variational approximation that allows scalable inference and learning of the model parameters. We demonstrate the power of the approach on two biological case studies, showing that the method allows a high degree of flexibility and is capable of testable novel biological predictions. http://homepages.inf.ed.ac.uk/gsanguin/software.html. Supplementary data are available at Bioinformatics online.
Application of structured support vector machine backpropagation to a convolutional neural network for human pose estimation.

PubMed

Witoonchart, Peerajak; Chongstitvatana, Prabhas

2017-08-01

In this study, for the first time, we show how to formulate a structured support vector machine (SSVM) as two layers in a convolutional neural network, where the top layer is a loss augmented inference layer and the bottom layer is the normal convolutional layer. We show that a deformable part model can be learned with the proposed structured SVM neural network by backpropagating the error of the deformable part model to the convolutional neural network. The forward propagation calculates the loss augmented inference and the backpropagation calculates the gradient from the loss augmented inference layer to the convolutional layer. Thus, we obtain a new type of convolutional neural network called an Structured SVM convolutional neural network, which we applied to the human pose estimation problem. This new neural network can be used as the final layers in deep learning. Our method jointly learns the structural model parameters and the appearance model parameters. We implemented our method as a new layer in the existing Caffe library. Copyright © 2017 Elsevier Ltd. All rights reserved.
Combining inferred regulatory and reconstructed metabolic networks enhances phenotype prediction in yeast.

PubMed

Wang, Zhuo; Danziger, Samuel A; Heavner, Benjamin D; Ma, Shuyi; Smith, Jennifer J; Li, Song; Herricks, Thurston; Simeonidis, Evangelos; Baliga, Nitin S; Aitchison, John D; Price, Nathan D

2017-05-01

Gene regulatory and metabolic network models have been used successfully in many organisms, but inherent differences between them make networks difficult to integrate. Probabilistic Regulation Of Metabolism (PROM) provides a partial solution, but it does not incorporate network inference and underperforms in eukaryotes. We present an Integrated Deduced And Metabolism (IDREAM) method that combines statistically inferred Environment and Gene Regulatory Influence Network (EGRIN) models with the PROM framework to create enhanced metabolic-regulatory network models. We used IDREAM to predict phenotypes and genetic interactions between transcription factors and genes encoding metabolic activities in the eukaryote, Saccharomyces cerevisiae. IDREAM models contain many fewer interactions than PROM and yet produce significantly more accurate growth predictions. IDREAM consistently outperformed PROM using any of three popular yeast metabolic models and across three experimental growth conditions. Importantly, IDREAM's enhanced accuracy makes it possible to identify subtle synthetic growth defects. With experimental validation, these novel genetic interactions involving the pyruvate dehydrogenase complex suggested a new role for fatty acid-responsive factor Oaf1 in regulating acetyl-CoA production in glucose grown cells.
Learning Probabilistic Inference through Spike-Timing-Dependent Plasticity.

PubMed

Pecevski, Dejan; Maass, Wolfgang

2016-01-01

Numerous experimental data show that the brain is able to extract information from complex, uncertain, and often ambiguous experiences. Furthermore, it can use such learnt information for decision making through probabilistic inference. Several models have been proposed that aim at explaining how probabilistic inference could be performed by networks of neurons in the brain. We propose here a model that can also explain how such neural network could acquire the necessary information for that from examples. We show that spike-timing-dependent plasticity in combination with intrinsic plasticity generates in ensembles of pyramidal cells with lateral inhibition a fundamental building block for that: probabilistic associations between neurons that represent through their firing current values of random variables. Furthermore, by combining such adaptive network motifs in a recursive manner the resulting network is enabled to extract statistical information from complex input streams, and to build an internal model for the distribution p (*) that generates the examples it receives. This holds even if p (*) contains higher-order moments. The analysis of this learning process is supported by a rigorous theoretical foundation. Furthermore, we show that the network can use the learnt internal model immediately for prediction, decision making, and other types of probabilistic inference.
Learning Probabilistic Inference through Spike-Timing-Dependent Plasticity123

PubMed Central

Pecevski, Dejan

2016-01-01

Abstract Numerous experimental data show that the brain is able to extract information from complex, uncertain, and often ambiguous experiences. Furthermore, it can use such learnt information for decision making through probabilistic inference. Several models have been proposed that aim at explaining how probabilistic inference could be performed by networks of neurons in the brain. We propose here a model that can also explain how such neural network could acquire the necessary information for that from examples. We show that spike-timing-dependent plasticity in combination with intrinsic plasticity generates in ensembles of pyramidal cells with lateral inhibition a fundamental building block for that: probabilistic associations between neurons that represent through their firing current values of random variables. Furthermore, by combining such adaptive network motifs in a recursive manner the resulting network is enabled to extract statistical information from complex input streams, and to build an internal model for the distribution p* that generates the examples it receives. This holds even if p* contains higher-order moments. The analysis of this learning process is supported by a rigorous theoretical foundation. Furthermore, we show that the network can use the learnt internal model immediately for prediction, decision making, and other types of probabilistic inference. PMID:27419214
Inferring Time-Varying Network Topologies from Gene Expression Data

PubMed Central

2007-01-01

Most current methods for gene regulatory network identification lead to the inference of steady-state networks, that is, networks prevalent over all times, a hypothesis which has been challenged. There has been a need to infer and represent networks in a dynamic, that is, time-varying fashion, in order to account for different cellular states affecting the interactions amongst genes. In this work, we present an approach, regime-SSM, to understand gene regulatory networks within such a dynamic setting. The approach uses a clustering method based on these underlying dynamics, followed by system identification using a state-space model for each learnt cluster—to infer a network adjacency matrix. We finally indicate our results on the mouse embryonic kidney dataset as well as the T-cell activation-based expression dataset and demonstrate conformity with reported experimental evidence. PMID:18309363
Inferring time-varying network topologies from gene expression data.

PubMed

Rao, Arvind; Hero, Alfred O; States, David J; Engel, James Douglas

2007-01-01

Most current methods for gene regulatory network identification lead to the inference of steady-state networks, that is, networks prevalent over all times, a hypothesis which has been challenged. There has been a need to infer and represent networks in a dynamic, that is, time-varying fashion, in order to account for different cellular states affecting the interactions amongst genes. In this work, we present an approach, regime-SSM, to understand gene regulatory networks within such a dynamic setting. The approach uses a clustering method based on these underlying dynamics, followed by system identification using a state-space model for each learnt cluster--to infer a network adjacency matrix. We finally indicate our results on the mouse embryonic kidney dataset as well as the T-cell activation-based expression dataset and demonstrate conformity with reported experimental evidence.

Successful Reconstruction of a Physiological Circuit with Known Connectivity from Spiking Activity Alone

PubMed Central

Gerhard, Felipe; Kispersky, Tilman; Gutierrez, Gabrielle J.; Marder, Eve; Kramer, Mark; Eden, Uri

2013-01-01

Identifying the structure and dynamics of synaptic interactions between neurons is the first step to understanding neural network dynamics. The presence of synaptic connections is traditionally inferred through the use of targeted stimulation and paired recordings or by post-hoc histology. More recently, causal network inference algorithms have been proposed to deduce connectivity directly from electrophysiological signals, such as extracellularly recorded spiking activity. Usually, these algorithms have not been validated on a neurophysiological data set for which the actual circuitry is known. Recent work has shown that traditional network inference algorithms based on linear models typically fail to identify the correct coupling of a small central pattern generating circuit in the stomatogastric ganglion of the crab Cancer borealis. In this work, we show that point process models of observed spike trains can guide inference of relative connectivity estimates that match the known physiological connectivity of the central pattern generator up to a choice of threshold. We elucidate the necessary steps to derive faithful connectivity estimates from a model that incorporates the spike train nature of the data. We then apply the model to measure changes in the effective connectivity pattern in response to two pharmacological interventions, which affect both intrinsic neural dynamics and synaptic transmission. Our results provide the first successful application of a network inference algorithm to a circuit for which the actual physiological synapses between neurons are known. The point process methodology presented here generalizes well to larger networks and can describe the statistics of neural populations. In general we show that advanced statistical models allow for the characterization of effective network structure, deciphering underlying network dynamics and estimating information-processing capabilities. PMID:23874181
minet: A R/Bioconductor package for inferring large transcriptional networks using mutual information.

PubMed

Meyer, Patrick E; Lafitte, Frédéric; Bontempi, Gianluca

2008-10-29

This paper presents the R/Bioconductor package minet (version 1.1.6) which provides a set of functions to infer mutual information networks from a dataset. Once fed with a microarray dataset, the package returns a network where nodes denote genes, edges model statistical dependencies between genes and the weight of an edge quantifies the statistical evidence of a specific (e.g transcriptional) gene-to-gene interaction. Four different entropy estimators are made available in the package minet (empirical, Miller-Madow, Schurmann-Grassberger and shrink) as well as four different inference methods, namely relevance networks, ARACNE, CLR and MRNET. Also, the package integrates accuracy assessment tools, like F-scores, PR-curves and ROC-curves in order to compare the inferred network with a reference one. The package minet provides a series of tools for inferring transcriptional networks from microarray data. It is freely available from the Comprehensive R Archive Network (CRAN) as well as from the Bioconductor website.
Consistency of biological networks inferred from microarray and sequencing data.

PubMed

Vinciotti, Veronica; Wit, Ernst C; Jansen, Rick; de Geus, Eco J C N; Penninx, Brenda W J H; Boomsma, Dorret I; 't Hoen, Peter A C

2016-06-24

Sparse Gaussian graphical models are popular for inferring biological networks, such as gene regulatory networks. In this paper, we investigate the consistency of these models across different data platforms, such as microarray and next generation sequencing, on the basis of a rich dataset containing samples that are profiled under both techniques as well as a large set of independent samples. Our analysis shows that individual node variances can have a remarkable effect on the connectivity of the resulting network. Their inconsistency across platforms and the fact that the variability level of a node may not be linked to its regulatory role mean that, failing to scale the data prior to the network analysis, leads to networks that are not reproducible across different platforms and that may be misleading. Moreover, we show how the reproducibility of networks across different platforms is significantly higher if networks are summarised in terms of enrichment amongst functional groups of interest, such as pathways, rather than at the level of individual edges. Careful pre-processing of transcriptional data and summaries of networks beyond individual edges can improve the consistency of network inference across platforms. However, caution is needed at this stage in the (over)interpretation of gene regulatory networks inferred from biological data.
Multi-Agent Inference in Social Networks: A Finite Population Learning Approach.

PubMed

Fan, Jianqing; Tong, Xin; Zeng, Yao

When people in a society want to make inference about some parameter, each person may want to use data collected by other people. Information (data) exchange in social networks is usually costly, so to make reliable statistical decisions, people need to trade off the benefits and costs of information acquisition. Conflicts of interests and coordination problems will arise in the process. Classical statistics does not consider people's incentives and interactions in the data collection process. To address this imperfection, this work explores multi-agent Bayesian inference problems with a game theoretic social network model. Motivated by our interest in aggregate inference at the societal level, we propose a new concept, finite population learning , to address whether with high probability, a large fraction of people in a given finite population network can make "good" inference. Serving as a foundation, this concept enables us to study the long run trend of aggregate inference quality as population grows.
Inferring causal molecular networks: empirical assessment through a community-based effort.

PubMed

Hill, Steven M; Heiser, Laura M; Cokelaer, Thomas; Unger, Michael; Nesser, Nicole K; Carlin, Daniel E; Zhang, Yang; Sokolov, Artem; Paull, Evan O; Wong, Chris K; Graim, Kiley; Bivol, Adrian; Wang, Haizhou; Zhu, Fan; Afsari, Bahman; Danilova, Ludmila V; Favorov, Alexander V; Lee, Wai Shing; Taylor, Dane; Hu, Chenyue W; Long, Byron L; Noren, David P; Bisberg, Alexander J; Mills, Gordon B; Gray, Joe W; Kellen, Michael; Norman, Thea; Friend, Stephen; Qutub, Amina A; Fertig, Elana J; Guan, Yuanfang; Song, Mingzhou; Stuart, Joshua M; Spellman, Paul T; Koeppl, Heinz; Stolovitzky, Gustavo; Saez-Rodriguez, Julio; Mukherjee, Sach

2016-04-01

It remains unclear whether causal, rather than merely correlational, relationships in molecular networks can be inferred in complex biological settings. Here we describe the HPN-DREAM network inference challenge, which focused on learning causal influences in signaling networks. We used phosphoprotein data from cancer cell lines as well as in silico data from a nonlinear dynamical model. Using the phosphoprotein data, we scored more than 2,000 networks submitted by challenge participants. The networks spanned 32 biological contexts and were scored in terms of causal validity with respect to unseen interventional data. A number of approaches were effective, and incorporating known biology was generally advantageous. Additional sub-challenges considered time-course prediction and visualization. Our results suggest that learning causal relationships may be feasible in complex settings such as disease states. Furthermore, our scoring approach provides a practical way to empirically assess inferred molecular networks in a causal sense.
Boosting probabilistic graphical model inference by incorporating prior knowledge from multiple sources.

PubMed

Praveen, Paurush; Fröhlich, Holger

2013-01-01

Inferring regulatory networks from experimental data via probabilistic graphical models is a popular framework to gain insights into biological systems. However, the inherent noise in experimental data coupled with a limited sample size reduces the performance of network reverse engineering. Prior knowledge from existing sources of biological information can address this low signal to noise problem by biasing the network inference towards biologically plausible network structures. Although integrating various sources of information is desirable, their heterogeneous nature makes this task challenging. We propose two computational methods to incorporate various information sources into a probabilistic consensus structure prior to be used in graphical model inference. Our first model, called Latent Factor Model (LFM), assumes a high degree of correlation among external information sources and reconstructs a hidden variable as a common source in a Bayesian manner. The second model, a Noisy-OR, picks up the strongest support for an interaction among information sources in a probabilistic fashion. Our extensive computational studies on KEGG signaling pathways as well as on gene expression data from breast cancer and yeast heat shock response reveal that both approaches can significantly enhance the reconstruction accuracy of Bayesian Networks compared to other competing methods as well as to the situation without any prior. Our framework allows for using diverse information sources, like pathway databases, GO terms and protein domain data, etc. and is flexible enough to integrate new sources, if available.
Modeling gene regulatory networks: A network simplification algorithm

NASA Astrophysics Data System (ADS)

Ferreira, Luiz Henrique O.; de Castro, Maria Clicia S.; da Silva, Fabricio A. B.

2016-12-01

Boolean networks have been used for some time to model Gene Regulatory Networks (GRNs), which describe cell functions. Those models can help biologists to make predictions, prognosis and even specialized treatment when some disturb on the GRN lead to a sick condition. However, the amount of information related to a GRN can be huge, making the task of inferring its boolean network representation quite a challenge. The method shown here takes into account information about the interactome to build a network, where each node represents a protein, and uses the entropy of each node as a key to reduce the size of the network, allowing the further inferring process to focus only on the main protein hubs, the ones with most potential to interfere in overall network behavior.
Dynamic modelling of microRNA regulation during mesenchymal stem cell differentiation.

PubMed

Weber, Michael; Sotoca, Ana M; Kupfer, Peter; Guthke, Reinhard; van Zoelen, Everardus J

2013-11-12

Network inference from gene expression data is a typical approach to reconstruct gene regulatory networks. During chondrogenic differentiation of human mesenchymal stem cells (hMSCs), a complex transcriptional network is active and regulates the temporal differentiation progress. As modulators of transcriptional regulation, microRNAs (miRNAs) play a critical role in stem cell differentiation. Integrated network inference aimes at determining interrelations between miRNAs and mRNAs on the basis of expression data as well as miRNA target predictions. We applied the NetGenerator tool in order to infer an integrated gene regulatory network. Time series experiments were performed to measure mRNA and miRNA abundances of TGF-beta1+BMP2 stimulated hMSCs. Network nodes were identified by analysing temporal expression changes, miRNA target gene predictions, time series correlation and literature knowledge. Network inference was performed using NetGenerator to reconstruct a dynamical regulatory model based on the measured data and prior knowledge. The resulting model is robust against noise and shows an optimal trade-off between fitting precision and inclusion of prior knowledge. It predicts the influence of miRNAs on the expression of chondrogenic marker genes and therefore proposes novel regulatory relations in differentiation control. By analysing the inferred network, we identified a previously unknown regulatory effect of miR-524-5p on the expression of the transcription factor SOX9 and the chondrogenic marker genes COL2A1, ACAN and COL10A1. Genome-wide exploration of miRNA-mRNA regulatory relationships is a reasonable approach to identify miRNAs which have so far not been associated with the investigated differentiation process. The NetGenerator tool is able to identify valid gene regulatory networks on the basis of miRNA and mRNA time series data.
An integrated approach to infer dynamic protein-gene interactions - A case study of the human P53 protein.

PubMed

Wang, Junbai; Wu, Qianqian; Hu, Xiaohua Tony; Tian, Tianhai

2016-11-01

Investigating the dynamics of genetic regulatory networks through high throughput experimental data, such as microarray gene expression profiles, is a very important but challenging task. One of the major hindrances in building detailed mathematical models for genetic regulation is the large number of unknown model parameters. To tackle this challenge, a new integrated method is proposed by combining a top-down approach and a bottom-up approach. First, the top-down approach uses probabilistic graphical models to predict the network structure of DNA repair pathway that is regulated by the p53 protein. Two networks are predicted, namely a network of eight genes with eight inferred interactions and an extended network of 21 genes with 17 interactions. Then, the bottom-up approach using differential equation models is developed to study the detailed genetic regulations based on either a fully connected regulatory network or a gene network obtained by the top-down approach. Model simulation error, parameter identifiability and robustness property are used as criteria to select the optimal network. Simulation results together with permutation tests of input gene network structures indicate that the prediction accuracy and robustness property of the two predicted networks using the top-down approach are better than those of the corresponding fully connected networks. In particular, the proposed approach reduces computational cost significantly for inferring model parameters. Overall, the new integrated method is a promising approach for investigating the dynamics of genetic regulation. Copyright © 2016 Elsevier Inc. All rights reserved.
Inferring network structure from cascades.

PubMed

Ghonge, Sushrut; Vural, Dervis Can

2017-07-01

Many physical, biological, and social phenomena can be described by cascades taking place on a network. Often, the activity can be empirically observed, but not the underlying network of interactions. In this paper we offer three topological methods to infer the structure of any directed network given a set of cascade arrival times. Our formulas hold for a very general class of models where the activation probability of a node is a generic function of its degree and the number of its active neighbors. We report high success rates for synthetic and real networks, for several different cascade models.
Inferring network structure from cascades

NASA Astrophysics Data System (ADS)

Ghonge, Sushrut; Vural, Dervis Can

2017-07-01

Many physical, biological, and social phenomena can be described by cascades taking place on a network. Often, the activity can be empirically observed, but not the underlying network of interactions. In this paper we offer three topological methods to infer the structure of any directed network given a set of cascade arrival times. Our formulas hold for a very general class of models where the activation probability of a node is a generic function of its degree and the number of its active neighbors. We report high success rates for synthetic and real networks, for several different cascade models.
Petri Nets with Fuzzy Logic (PNFL): Reverse Engineering and Parametrization

PubMed Central

Küffner, Robert; Petri, Tobias; Windhager, Lukas; Zimmer, Ralf

2010-01-01

Background The recent DREAM4 blind assessment provided a particularly realistic and challenging setting for network reverse engineering methods. The in silico part of DREAM4 solicited the inference of cycle-rich gene regulatory networks from heterogeneous, noisy expression data including time courses as well as knockout, knockdown and multifactorial perturbations. Methodology and Principal Findings We inferred and parametrized simulation models based on Petri Nets with Fuzzy Logic (PNFL). This completely automated approach correctly reconstructed networks with cycles as well as oscillating network motifs. PNFL was evaluated as the best performer on DREAM4 in silico networks of size 10 with an area under the precision-recall curve (AUPR) of 81%. Besides topology, we inferred a range of additional mechanistic details with good reliability, e.g. distinguishing activation from inhibition as well as dependent from independent regulation. Our models also performed well on new experimental conditions such as double knockout mutations that were not included in the provided datasets. Conclusions The inference of biological networks substantially benefits from methods that are expressive enough to deal with diverse datasets in a unified way. At the same time, overly complex approaches could generate multiple different models that explain the data equally well. PNFL appears to strike the balance between expressive power and complexity. This also applies to the intuitive representation of PNFL models combining a straightforward graphical notation with colloquial fuzzy parameters. PMID:20862218
Spiking neuron network Helmholtz machine.

PubMed

Sountsov, Pavel; Miller, Paul

2015-01-01

An increasing amount of behavioral and neurophysiological data suggests that the brain performs optimal (or near-optimal) probabilistic inference and learning during perception and other tasks. Although many machine learning algorithms exist that perform inference and learning in an optimal way, the complete description of how one of those algorithms (or a novel algorithm) can be implemented in the brain is currently incomplete. There have been many proposed solutions that address how neurons can perform optimal inference but the question of how synaptic plasticity can implement optimal learning is rarely addressed. This paper aims to unify the two fields of probabilistic inference and synaptic plasticity by using a neuronal network of realistic model spiking neurons to implement a well-studied computational model called the Helmholtz Machine. The Helmholtz Machine is amenable to neural implementation as the algorithm it uses to learn its parameters, called the wake-sleep algorithm, uses a local delta learning rule. Our spiking-neuron network implements both the delta rule and a small example of a Helmholtz machine. This neuronal network can learn an internal model of continuous-valued training data sets without supervision. The network can also perform inference on the learned internal models. We show how various biophysical features of the neural implementation constrain the parameters of the wake-sleep algorithm, such as the duration of the wake and sleep phases of learning and the minimal sample duration. We examine the deviations from optimal performance and tie them to the properties of the synaptic plasticity rule.
Spiking neuron network Helmholtz machine

PubMed Central

Sountsov, Pavel; Miller, Paul

2015-01-01

An increasing amount of behavioral and neurophysiological data suggests that the brain performs optimal (or near-optimal) probabilistic inference and learning during perception and other tasks. Although many machine learning algorithms exist that perform inference and learning in an optimal way, the complete description of how one of those algorithms (or a novel algorithm) can be implemented in the brain is currently incomplete. There have been many proposed solutions that address how neurons can perform optimal inference but the question of how synaptic plasticity can implement optimal learning is rarely addressed. This paper aims to unify the two fields of probabilistic inference and synaptic plasticity by using a neuronal network of realistic model spiking neurons to implement a well-studied computational model called the Helmholtz Machine. The Helmholtz Machine is amenable to neural implementation as the algorithm it uses to learn its parameters, called the wake-sleep algorithm, uses a local delta learning rule. Our spiking-neuron network implements both the delta rule and a small example of a Helmholtz machine. This neuronal network can learn an internal model of continuous-valued training data sets without supervision. The network can also perform inference on the learned internal models. We show how various biophysical features of the neural implementation constrain the parameters of the wake-sleep algorithm, such as the duration of the wake and sleep phases of learning and the minimal sample duration. We examine the deviations from optimal performance and tie them to the properties of the synaptic plasticity rule. PMID:25954191
Deep Unfolding for Topic Models.

PubMed

Chien, Jen-Tzung; Lee, Chao-Hsi

2018-02-01

Deep unfolding provides an approach to integrate the probabilistic generative models and the deterministic neural networks. Such an approach is benefited by deep representation, easy interpretation, flexible learning and stochastic modeling. This study develops the unsupervised and supervised learning of deep unfolded topic models for document representation and classification. Conventionally, the unsupervised and supervised topic models are inferred via the variational inference algorithm where the model parameters are estimated by maximizing the lower bound of logarithm of marginal likelihood using input documents without and with class labels, respectively. The representation capability or classification accuracy is constrained by the variational lower bound and the tied model parameters across inference procedure. This paper aims to relax these constraints by directly maximizing the end performance criterion and continuously untying the parameters in learning process via deep unfolding inference (DUI). The inference procedure is treated as the layer-wise learning in a deep neural network. The end performance is iteratively improved by using the estimated topic parameters according to the exponentiated updates. Deep learning of topic models is therefore implemented through a back-propagation procedure. Experimental results show the merits of DUI with increasing number of layers compared with variational inference in unsupervised as well as supervised topic models.
A Machine Learning Approach to Predict Gene Regulatory Networks in Seed Development in Arabidopsis

PubMed Central

Ni, Ying; Aghamirzaie, Delasa; Elmarakeby, Haitham; Collakova, Eva; Li, Song; Grene, Ruth; Heath, Lenwood S.

2016-01-01

Gene regulatory networks (GRNs) provide a representation of relationships between regulators and their target genes. Several methods for GRN inference, both unsupervised and supervised, have been developed to date. Because regulatory relationships consistently reprogram in diverse tissues or under different conditions, GRNs inferred without specific biological contexts are of limited applicability. In this report, a machine learning approach is presented to predict GRNs specific to developing Arabidopsis thaliana embryos. We developed the Beacon GRN inference tool to predict GRNs occurring during seed development in Arabidopsis based on a support vector machine (SVM) model. We developed both global and local inference models and compared their performance, demonstrating that local models are generally superior for our application. Using both the expression levels of the genes expressed in developing embryos and prior known regulatory relationships, GRNs were predicted for specific embryonic developmental stages. The targets that are strongly positively correlated with their regulators are mostly expressed at the beginning of seed development. Potential direct targets were identified based on a match between the promoter regions of these inferred targets and the cis elements recognized by specific regulators. Our analysis also provides evidence for previously unknown inhibitory effects of three positive regulators of gene expression. The Beacon GRN inference tool provides a valuable model system for context-specific GRN inference and is freely available at https://github.com/BeaconProjectAtVirginiaTech/beacon_network_inference.git. PMID:28066488
GeneNetWeaver: in silico benchmark generation and performance profiling of network inference methods.

PubMed

Schaffter, Thomas; Marbach, Daniel; Floreano, Dario

2011-08-15

Over the last decade, numerous methods have been developed for inference of regulatory networks from gene expression data. However, accurate and systematic evaluation of these methods is hampered by the difficulty of constructing adequate benchmarks and the lack of tools for a differentiated analysis of network predictions on such benchmarks. Here, we describe a novel and comprehensive method for in silico benchmark generation and performance profiling of network inference methods available to the community as an open-source software called GeneNetWeaver (GNW). In addition to the generation of detailed dynamical models of gene regulatory networks to be used as benchmarks, GNW provides a network motif analysis that reveals systematic prediction errors, thereby indicating potential ways of improving inference methods. The accuracy of network inference methods is evaluated using standard metrics such as precision-recall and receiver operating characteristic curves. We show how GNW can be used to assess the performance and identify the strengths and weaknesses of six inference methods. Furthermore, we used GNW to provide the international Dialogue for Reverse Engineering Assessments and Methods (DREAM) competition with three network inference challenges (DREAM3, DREAM4 and DREAM5). GNW is available at http://gnw.sourceforge.net along with its Java source code, user manual and supporting data. Supplementary data are available at Bioinformatics online. dario.floreano@epfl.ch.
Gene expression complex networks: synthesis, identification, and analysis.

PubMed

Lopes, Fabrício M; Cesar, Roberto M; Costa, Luciano Da F

2011-10-01

Thanks to recent advances in molecular biology, allied to an ever increasing amount of experimental data, the functional state of thousands of genes can now be extracted simultaneously by using methods such as cDNA microarrays and RNA-Seq. Particularly important related investigations are the modeling and identification of gene regulatory networks from expression data sets. Such a knowledge is fundamental for many applications, such as disease treatment, therapeutic intervention strategies and drugs design, as well as for planning high-throughput new experiments. Methods have been developed for gene networks modeling and identification from expression profiles. However, an important open problem regards how to validate such approaches and its results. This work presents an objective approach for validation of gene network modeling and identification which comprises the following three main aspects: (1) Artificial Gene Networks (AGNs) model generation through theoretical models of complex networks, which is used to simulate temporal expression data; (2) a computational method for gene network identification from the simulated data, which is founded on a feature selection approach where a target gene is fixed and the expression profile is observed for all other genes in order to identify a relevant subset of predictors; and (3) validation of the identified AGN-based network through comparison with the original network. The proposed framework allows several types of AGNs to be generated and used in order to simulate temporal expression data. The results of the network identification method can then be compared to the original network in order to estimate its properties and accuracy. Some of the most important theoretical models of complex networks have been assessed: the uniformly-random Erdös-Rényi (ER), the small-world Watts-Strogatz (WS), the scale-free Barabási-Albert (BA), and geographical networks (GG). The experimental results indicate that the inference method was sensitive to average degree variation, decreasing its network recovery rate with the increase of . The signal size was important for the inference method to get better accuracy in the network identification rate, presenting very good results with small expression profiles. However, the adopted inference method was not sensible to recognize distinct structures of interaction among genes, presenting a similar behavior when applied to different network topologies. In summary, the proposed framework, though simple, was adequate for the validation of the inferred networks by identifying some properties of the evaluated method, which can be extended to other inference methods.
Probabilistic inference in discrete spaces can be implemented into networks of LIF neurons.

PubMed

Probst, Dimitri; Petrovici, Mihai A; Bytschok, Ilja; Bill, Johannes; Pecevski, Dejan; Schemmel, Johannes; Meier, Karlheinz

2015-01-01

The means by which cortical neural networks are able to efficiently solve inference problems remains an open question in computational neuroscience. Recently, abstract models of Bayesian computation in neural circuits have been proposed, but they lack a mechanistic interpretation at the single-cell level. In this article, we describe a complete theoretical framework for building networks of leaky integrate-and-fire neurons that can sample from arbitrary probability distributions over binary random variables. We test our framework for a model inference task based on a psychophysical phenomenon (the Knill-Kersten optical illusion) and further assess its performance when applied to randomly generated distributions. As the local computations performed by the network strongly depend on the interaction between neurons, we compare several types of couplings mediated by either single synapses or interneuron chains. Due to its robustness to substrate imperfections such as parameter noise and background noise correlations, our model is particularly interesting for implementation on novel, neuro-inspired computing architectures, which can thereby serve as a fast, low-power substrate for solving real-world inference problems.
Probabilistic inference in discrete spaces can be implemented into networks of LIF neurons

PubMed Central

Probst, Dimitri; Petrovici, Mihai A.; Bytschok, Ilja; Bill, Johannes; Pecevski, Dejan; Schemmel, Johannes; Meier, Karlheinz

2015-01-01

The means by which cortical neural networks are able to efficiently solve inference problems remains an open question in computational neuroscience. Recently, abstract models of Bayesian computation in neural circuits have been proposed, but they lack a mechanistic interpretation at the single-cell level. In this article, we describe a complete theoretical framework for building networks of leaky integrate-and-fire neurons that can sample from arbitrary probability distributions over binary random variables. We test our framework for a model inference task based on a psychophysical phenomenon (the Knill-Kersten optical illusion) and further assess its performance when applied to randomly generated distributions. As the local computations performed by the network strongly depend on the interaction between neurons, we compare several types of couplings mediated by either single synapses or interneuron chains. Due to its robustness to substrate imperfections such as parameter noise and background noise correlations, our model is particularly interesting for implementation on novel, neuro-inspired computing architectures, which can thereby serve as a fast, low-power substrate for solving real-world inference problems. PMID:25729361

Effects of spatial constraints on channel network topology: Implications for geomorphological inference

NASA Astrophysics Data System (ADS)

Cabral, Mariza Castanheira De Moura Da Costa

In the fifty-two years since Robert Horton's 1945 pioneering quantitative description of channel network planform (or plan view morphology), no conclusive findings have been presented that permit inference of geomorphological processes from any measures of network planform. All measures of network planform studied exhibit limited geographic variability across different environments. Horton (1945), Langbein et al. (1947), Schumm (1956), Hack (1957), Melton (1958), and Gray (1961) established various "laws" of network planform, that is, statistical relationships between different variables which have limited variability. A wide variety of models which have been proposed to simulate the growth of channel networks in time over a landsurface are generally also in agreement with the above planform laws. An explanation is proposed for the generality of the channel network planform laws. Channel networks must be space filling, that is, they must extend over the landscape to drain every hillslope, leaving no large undrained areas, and with no crossing of channels, often achieving a roughly uniform drainage density in a given environment. It is shown that the space-filling constraint can reduce the sensitivity of planform variables to different network growth models, and it is proposed that this constraint may determine the planform laws. The "Q model" of network growth of Van Pelt and Verwer (1985) is used to generate samples of networks. Sensitivity to the model parameter Q is markedly reduced when the networks generated are required to be space filling. For a wide variety of Q values, the space-filling networks are in approximate agreement with the various channel network planform laws. Additional constraints, including of energy efficiency, were not studied but may further reduce the variability of planform laws. Inference of model parameter Q from network topology is successful only in networks not subject to spatial constraints. In space-filling networks, for a wide range of Q values, the maximal-likelihood Q parameter value is generally in the vicinity of 1/2, which yields topological randomness. It is proposed that space filling originates the appearance of randomness in channel network topology, and may cause difficulties to geomorphological inference from network planform.
Inference of Gene Regulatory Networks Using Time-Series Data: A Survey

PubMed Central

Sima, Chao; Hua, Jianping; Jung, Sungwon

2009-01-01

The advent of high-throughput technology like microarrays has provided the platform for studying how different cellular components work together, thus created an enormous interest in mathematically modeling biological network, particularly gene regulatory network (GRN). Of particular interest is the modeling and inference on time-series data, which capture a more thorough picture of the system than non-temporal data do. We have given an extensive review of methodologies that have been used on time-series data. In realizing that validation is an impartible part of the inference paradigm, we have also presented a discussion on the principles and challenges in performance evaluation of different methods. This survey gives a panoramic view on these topics, with anticipation that the readers will be inspired to improve and/or expand GRN inference and validation tool repository. PMID:20190956
Bayesian parameter inference for stochastic biochemical network models using particle Markov chain Monte Carlo

PubMed Central

Golightly, Andrew; Wilkinson, Darren J.

2011-01-01

Computational systems biology is concerned with the development of detailed mechanistic models of biological processes. Such models are often stochastic and analytically intractable, containing uncertain parameters that must be estimated from time course data. In this article, we consider the task of inferring the parameters of a stochastic kinetic model defined as a Markov (jump) process. Inference for the parameters of complex nonlinear multivariate stochastic process models is a challenging problem, but we find here that algorithms based on particle Markov chain Monte Carlo turn out to be a very effective computationally intensive approach to the problem. Approximations to the inferential model based on stochastic differential equations (SDEs) are considered, as well as improvements to the inference scheme that exploit the SDE structure. We apply the methodology to a Lotka–Volterra system and a prokaryotic auto-regulatory network. PMID:23226583
Multi-Agent Inference in Social Networks: A Finite Population Learning Approach

PubMed Central

Tong, Xin; Zeng, Yao

2016-01-01

When people in a society want to make inference about some parameter, each person may want to use data collected by other people. Information (data) exchange in social networks is usually costly, so to make reliable statistical decisions, people need to trade off the benefits and costs of information acquisition. Conflicts of interests and coordination problems will arise in the process. Classical statistics does not consider people’s incentives and interactions in the data collection process. To address this imperfection, this work explores multi-agent Bayesian inference problems with a game theoretic social network model. Motivated by our interest in aggregate inference at the societal level, we propose a new concept, finite population learning, to address whether with high probability, a large fraction of people in a given finite population network can make “good” inference. Serving as a foundation, this concept enables us to study the long run trend of aggregate inference quality as population grows. PMID:27076691
Boosting Probabilistic Graphical Model Inference by Incorporating Prior Knowledge from Multiple Sources

PubMed Central

Praveen, Paurush; Fröhlich, Holger

2013-01-01

Inferring regulatory networks from experimental data via probabilistic graphical models is a popular framework to gain insights into biological systems. However, the inherent noise in experimental data coupled with a limited sample size reduces the performance of network reverse engineering. Prior knowledge from existing sources of biological information can address this low signal to noise problem by biasing the network inference towards biologically plausible network structures. Although integrating various sources of information is desirable, their heterogeneous nature makes this task challenging. We propose two computational methods to incorporate various information sources into a probabilistic consensus structure prior to be used in graphical model inference. Our first model, called Latent Factor Model (LFM), assumes a high degree of correlation among external information sources and reconstructs a hidden variable as a common source in a Bayesian manner. The second model, a Noisy-OR, picks up the strongest support for an interaction among information sources in a probabilistic fashion. Our extensive computational studies on KEGG signaling pathways as well as on gene expression data from breast cancer and yeast heat shock response reveal that both approaches can significantly enhance the reconstruction accuracy of Bayesian Networks compared to other competing methods as well as to the situation without any prior. Our framework allows for using diverse information sources, like pathway databases, GO terms and protein domain data, etc. and is flexible enough to integrate new sources, if available. PMID:23826291
DEFINING THE PLAYERS IN HIGHER-ORDER NETWORKS: PREDICTIVE MODELING FOR REVERSE ENGINEERING FUNCTIONAL INFLUENCE NETWORKS

DOE Office of Scientific and Technical Information (OSTI.GOV)

McDermott, Jason E.; Costa, Michelle N.; Stevens, S.L.

A difficult problem that is currently growing rapidly due to the sharp increase in the amount of high-throughput data available for many systems is that of determining useful and informative causative influence networks. These networks can be used to predict behavior given observation of a small number of components, predict behavior at a future time point, or identify components that are critical to the functioning of the system under particular conditions. In these endeavors incorporating observations of systems from a wide variety of viewpoints can be particularly beneficial, but has often been undertaken with the objective of inferring networks thatmore » are generally applicable. The focus of the current work is to integrate both general observations and measurements taken for a particular pathology, that of ischemic stroke, to provide improved ability to produce useful predictions of systems behavior. A number of hybrid approaches have recently been proposed for network generation in which the Gene Ontology is used to filter or enrich network links inferred from gene expression data through reverse engineering methods. These approaches have been shown to improve the biological plausibility of the inferred relationships determined, but still treat knowledge-based and machine-learning inferences as incommensurable inputs. In this paper, we explore how further improvements may be achieved through a full integration of network inference insights achieved through application of the Gene Ontology and reverse engineering methods with specific reference to the construction of dynamic models of transcriptional regulatory networks. We show that integrating two approaches to network construction, one based on reverse-engineering from conditional transcriptional data, one based on reverse-engineering from in situ hybridization data, and another based on functional associations derived from Gene Ontology, using probabilities can improve results of clustering as evaluated by a predictive model of transcriptional expression levels.« less
A Scalable Approach to Probabilistic Latent Space Inference of Large-Scale Networks

PubMed Central

Yin, Junming; Ho, Qirong; Xing, Eric P.

2014-01-01

We propose a scalable approach for making inference about latent spaces of large networks. With a succinct representation of networks as a bag of triangular motifs, a parsimonious statistical model, and an efficient stochastic variational inference algorithm, we are able to analyze real networks with over a million vertices and hundreds of latent roles on a single machine in a matter of hours, a setting that is out of reach for many existing methods. When compared to the state-of-the-art probabilistic approaches, our method is several orders of magnitude faster, with competitive or improved accuracy for latent space recovery and link prediction. PMID:25400487
Model-free inference of direct network interactions from nonlinear collective dynamics.

PubMed

Casadiego, Jose; Nitzan, Mor; Hallerberg, Sarah; Timme, Marc

2017-12-19

The topology of interactions in network dynamical systems fundamentally underlies their function. Accelerating technological progress creates massively available data about collective nonlinear dynamics in physical, biological, and technological systems. Detecting direct interaction patterns from those dynamics still constitutes a major open problem. In particular, current nonlinear dynamics approaches mostly require to know a priori a model of the (often high dimensional) system dynamics. Here we develop a model-independent framework for inferring direct interactions solely from recording the nonlinear collective dynamics generated. Introducing an explicit dependency matrix in combination with a block-orthogonal regression algorithm, the approach works reliably across many dynamical regimes, including transient dynamics toward steady states, periodic and non-periodic dynamics, and chaos. Together with its capabilities to reveal network (two point) as well as hypernetwork (e.g., three point) interactions, this framework may thus open up nonlinear dynamics options of inferring direct interaction patterns across systems where no model is known.
Mapping the ecological networks of microbial communities.

PubMed

Xiao, Yandong; Angulo, Marco Tulio; Friedman, Jonathan; Waldor, Matthew K; Weiss, Scott T; Liu, Yang-Yu

2017-12-11

Mapping the ecological networks of microbial communities is a necessary step toward understanding their assembly rules and predicting their temporal behavior. However, existing methods require assuming a particular population dynamics model, which is not known a priori. Moreover, those methods require fitting longitudinal abundance data, which are often not informative enough for reliable inference. To overcome these limitations, here we develop a new method based on steady-state abundance data. Our method can infer the network topology and inter-taxa interaction types without assuming any particular population dynamics model. Additionally, when the population dynamics is assumed to follow the classic Generalized Lotka-Volterra model, our method can infer the inter-taxa interaction strengths and intrinsic growth rates. We systematically validate our method using simulated data, and then apply it to four experimental data sets. Our method represents a key step towards reliable modeling of complex, real-world microbial communities, such as the human gut microbiota.
Modeling Diagnostic Assessments with Bayesian Networks

ERIC Educational Resources Information Center

Almond, Russell G.; DiBello, Louis V.; Moulder, Brad; Zapata-Rivera, Juan-Diego

2007-01-01

This paper defines Bayesian network models and examines their applications to IRT-based cognitive diagnostic modeling. These models are especially suited to building inference engines designed to be synchronous with the finer grained student models that arise in skills diagnostic assessment. Aspects of the theory and use of Bayesian network models…
Deconvolution of mixing time series on a graph

PubMed Central

Blocker, Alexander W.; Airoldi, Edoardo M.

2013-01-01

In many applications we are interested in making inference on latent time series from indirect measurements, which are often low-dimensional projections resulting from mixing or aggregation. Positron emission tomography, super-resolution, and network traffic monitoring are some examples. Inference in such settings requires solving a sequence of ill-posed inverse problems, yt = Axt, where the projection mechanism provides information on A. We consider problems in which A specifies mixing on a graph of times series that are bursty and sparse. We develop a multilevel state-space model for mixing times series and an efficient approach to inference. A simple model is used to calibrate regularization parameters that lead to efficient inference in the multilevel state-space model. We apply this method to the problem of estimating point-to-point traffic flows on a network from aggregate measurements. Our solution outperforms existing methods for this problem, and our two-stage approach suggests an efficient inference strategy for multilevel models of multivariate time series. PMID:25309135
Generative models for discovering sparse distributed representations.

PubMed Central

Hinton, G E; Ghahramani, Z

1997-01-01

We describe a hierarchical, generative model that can be viewed as a nonlinear generalization of factor analysis and can be implemented in a neural network. The model uses bottom-up, top-down and lateral connections to perform Bayesian perceptual inference correctly. Once perceptual inference has been performed the connection strengths can be updated using a very simple learning rule that only requires locally available information. We demonstrate that the network learns to extract sparse, distributed, hierarchical representations. PMID:9304685
A New Modified Histogram Matching Normalization for Time Series Microarray Analysis.

PubMed

Astola, Laura; Molenaar, Jaap

2014-07-01

Microarray data is often utilized in inferring regulatory networks. Quantile normalization (QN) is a popular method to reduce array-to-array variation. We show that in the context of time series measurements QN may not be the best choice for this task, especially not if the inference is based on continuous time ODE model. We propose an alternative normalization method that is better suited for network inference from time series data.
Clustering network layers with the strata multilayer stochastic block model.

PubMed

Stanley, Natalie; Shai, Saray; Taylor, Dane; Mucha, Peter J

2016-01-01

Multilayer networks are a useful data structure for simultaneously capturing multiple types of relationships between a set of nodes. In such networks, each relational definition gives rise to a layer. While each layer provides its own set of information, community structure across layers can be collectively utilized to discover and quantify underlying relational patterns between nodes. To concisely extract information from a multilayer network, we propose to identify and combine sets of layers with meaningful similarities in community structure. In this paper, we describe the "strata multilayer stochastic block model" (sMLSBM), a probabilistic model for multilayer community structure. The central extension of the model is that there exist groups of layers, called "strata", which are defined such that all layers in a given stratum have community structure described by a common stochastic block model (SBM). That is, layers in a stratum exhibit similar node-to-community assignments and SBM probability parameters. Fitting the sMLSBM to a multilayer network provides a joint clustering that yields node-to-community and layer-to-stratum assignments, which cooperatively aid one another during inference. We describe an algorithm for separating layers into their appropriate strata and an inference technique for estimating the SBM parameters for each stratum. We demonstrate our method using synthetic networks and a multilayer network inferred from data collected in the Human Microbiome Project.
Macrostructure from Microstructure: Generating Whole Systems from Ego Networks

PubMed Central

Smith, Jeffrey A.

2014-01-01

This paper presents a new simulation method to make global network inference from sampled data. The proposed simulation method takes sampled ego network data and uses Exponential Random Graph Models (ERGM) to reconstruct the features of the true, unknown network. After describing the method, the paper presents two validity checks of the approach: the first uses the 20 largest Add Health networks while the second uses the Sociology Coauthorship network in the 1990's. For each test, I take random ego network samples from the known networks and use my method to make global network inference. I find that my method successfully reproduces the properties of the networks, such as distance and main component size. The results also suggest that simpler, baseline models provide considerably worse estimates for most network properties. I end the paper by discussing the bounds/limitations of ego network sampling. I also discuss possible extensions to the proposed approach. PMID:25339783
Inferring multi-scale neural mechanisms with brain network modelling

PubMed Central

Schirner, Michael; McIntosh, Anthony Randal; Jirsa, Viktor; Deco, Gustavo

2018-01-01

The neurophysiological processes underlying non-invasive brain activity measurements are incompletely understood. Here, we developed a connectome-based brain network model that integrates individual structural and functional data with neural population dynamics to support multi-scale neurophysiological inference. Simulated populations were linked by structural connectivity and, as a novelty, driven by electroencephalography (EEG) source activity. Simulations not only predicted subjects' individual resting-state functional magnetic resonance imaging (fMRI) time series and spatial network topologies over 20 minutes of activity, but more importantly, they also revealed precise neurophysiological mechanisms that underlie and link six empirical observations from different scales and modalities: (1) resting-state fMRI oscillations, (2) functional connectivity networks, (3) excitation-inhibition balance, (4, 5) inverse relationships between α-rhythms, spike-firing and fMRI on short and long time scales, and (6) fMRI power-law scaling. These findings underscore the potential of this new modelling framework for general inference and integration of neurophysiological knowledge to complement empirical studies. PMID:29308767
Genetic Network Inference: From Co-Expression Clustering to Reverse Engineering

NASA Technical Reports Server (NTRS)

Dhaeseleer, Patrik; Liang, Shoudan; Somogyi, Roland

2000-01-01

Advances in molecular biological, analytical, and computational technologies are enabling us to systematically investigate the complex molecular processes underlying biological systems. In particular, using high-throughput gene expression assays, we are able to measure the output of the gene regulatory network. We aim here to review datamining and modeling approaches for conceptualizing and unraveling the functional relationships implicit in these datasets. Clustering of co-expression profiles allows us to infer shared regulatory inputs and functional pathways. We discuss various aspects of clustering, ranging from distance measures to clustering algorithms and multiple-duster memberships. More advanced analysis aims to infer causal connections between genes directly, i.e., who is regulating whom and how. We discuss several approaches to the problem of reverse engineering of genetic networks, from discrete Boolean networks, to continuous linear and non-linear models. We conclude that the combination of predictive modeling with systematic experimental verification will be required to gain a deeper insight into living organisms, therapeutic targeting, and bioengineering.
Model-based redesign of global transcription regulation

PubMed Central

Carrera, Javier; Rodrigo, Guillermo; Jaramillo, Alfonso

2009-01-01

Synthetic biology aims to the design or redesign of biological systems. In particular, one possible goal could be the rewiring of the transcription regulation network by exchanging the endogenous promoters. To achieve this objective, we have adapted current methods to the inference of a model based on ordinary differential equations that is able to predict the network response after a major change in its topology. Our procedure utilizes microarray data for training. We have experimentally validated our inferred global regulatory model in Escherichia coli by predicting transcriptomic profiles under new perturbations. We have also tested our methodology in silico by providing accurate predictions of the underlying networks from expression data generated with artificial genomes. In addition, we have shown the predictive power of our methodology by obtaining the gene profile in experimental redesigns of the E. coli genome, where rewiring the transcriptional network by means of knockouts of master regulators or by upregulating transcription factors controlled by different promoters. Our approach is compatible with most network inference methods, allowing to explore computationally future genome-wide redesign experiments in synthetic biology. PMID:19188257
MORE: mixed optimization for reverse engineering--an application to modeling biological networks response via sparse systems of nonlinear differential equations.

PubMed

Sambo, Francesco; de Oca, Marco A Montes; Di Camillo, Barbara; Toffolo, Gianna; Stützle, Thomas

2012-01-01

Reverse engineering is the problem of inferring the structure of a network of interactions between biological variables from a set of observations. In this paper, we propose an optimization algorithm, called MORE, for the reverse engineering of biological networks from time series data. The model inferred by MORE is a sparse system of nonlinear differential equations, complex enough to realistically describe the dynamics of a biological system. MORE tackles separately the discrete component of the problem, the determination of the biological network topology, and the continuous component of the problem, the strength of the interactions. This approach allows us both to enforce system sparsity, by globally constraining the number of edges, and to integrate a priori information about the structure of the underlying interaction network. Experimental results on simulated and real-world networks show that the mixed discrete/continuous optimization approach of MORE significantly outperforms standard continuous optimization and that MORE is competitive with the state of the art in terms of accuracy of the inferred networks.
Integration of multi-omics data for integrative gene regulatory network inference.

PubMed

Zarayeneh, Neda; Ko, Euiseong; Oh, Jung Hun; Suh, Sang; Liu, Chunyu; Gao, Jean; Kim, Donghyun; Kang, Mingon

2017-01-01

Gene regulatory networks provide comprehensive insights and indepth understanding of complex biological processes. The molecular interactions of gene regulatory networks are inferred from a single type of genomic data, e.g., gene expression data in most research. However, gene expression is a product of sequential interactions of multiple biological processes, such as DNA sequence variations, copy number variations, histone modifications, transcription factors, and DNA methylations. The recent rapid advances of high-throughput omics technologies enable one to measure multiple types of omics data, called 'multi-omics data', that represent the various biological processes. In this paper, we propose an Integrative Gene Regulatory Network inference method (iGRN) that incorporates multi-omics data and their interactions in gene regulatory networks. In addition to gene expressions, copy number variations and DNA methylations were considered for multi-omics data in this paper. The intensive experiments were carried out with simulation data, where iGRN's capability that infers the integrative gene regulatory network is assessed. Through the experiments, iGRN shows its better performance on model representation and interpretation than other integrative methods in gene regulatory network inference. iGRN was also applied to a human brain dataset of psychiatric disorders, and the biological network of psychiatric disorders was analysed.

Integration of multi-omics data for integrative gene regulatory network inference

PubMed Central

Zarayeneh, Neda; Ko, Euiseong; Oh, Jung Hun; Suh, Sang; Liu, Chunyu; Gao, Jean; Kim, Donghyun

2017-01-01

Gene regulatory networks provide comprehensive insights and indepth understanding of complex biological processes. The molecular interactions of gene regulatory networks are inferred from a single type of genomic data, e.g., gene expression data in most research. However, gene expression is a product of sequential interactions of multiple biological processes, such as DNA sequence variations, copy number variations, histone modifications, transcription factors, and DNA methylations. The recent rapid advances of high-throughput omics technologies enable one to measure multiple types of omics data, called ‘multi-omics data’, that represent the various biological processes. In this paper, we propose an Integrative Gene Regulatory Network inference method (iGRN) that incorporates multi-omics data and their interactions in gene regulatory networks. In addition to gene expressions, copy number variations and DNA methylations were considered for multi-omics data in this paper. The intensive experiments were carried out with simulation data, where iGRN’s capability that infers the integrative gene regulatory network is assessed. Through the experiments, iGRN shows its better performance on model representation and interpretation than other integrative methods in gene regulatory network inference. iGRN was also applied to a human brain dataset of psychiatric disorders, and the biological network of psychiatric disorders was analysed. PMID:29354189
Recurrent neural network-based modeling of gene regulatory network using elephant swarm water search algorithm.

PubMed

Mandal, Sudip; Saha, Goutam; Pal, Rajat Kumar

2017-08-01

Correct inference of genetic regulations inside a cell from the biological database like time series microarray data is one of the greatest challenges in post genomic era for biologists and researchers. Recurrent Neural Network (RNN) is one of the most popular and simple approach to model the dynamics as well as to infer correct dependencies among genes. Inspired by the behavior of social elephants, we propose a new metaheuristic namely Elephant Swarm Water Search Algorithm (ESWSA) to infer Gene Regulatory Network (GRN). This algorithm is mainly based on the water search strategy of intelligent and social elephants during drought, utilizing the different types of communication techniques. Initially, the algorithm is tested against benchmark small and medium scale artificial genetic networks without and with presence of different noise levels and the efficiency was observed in term of parametric error, minimum fitness value, execution time, accuracy of prediction of true regulation, etc. Next, the proposed algorithm is tested against the real time gene expression data of Escherichia Coli SOS Network and results were also compared with others state of the art optimization methods. The experimental results suggest that ESWSA is very efficient for GRN inference problem and performs better than other methods in many ways.
Use of Network Inference to Elucidate Common and Chemical-specific Effects on Steoidogenesis

EPA Science Inventory

Microarray data is a key source for modeling gene regulatory interactions. Regulatory network models based on multiple datasets are potentially more robust and can provide greater confidence. In this study, we used network modeling on microarray data generated by exposing the fat...
Discriminative Relational Topic Models.

PubMed

Chen, Ning; Zhu, Jun; Xia, Fei; Zhang, Bo

2015-05-01

Relational topic models (RTMs) provide a probabilistic generative process to describe both the link structure and document contents for document networks, and they have shown promise on predicting network structures and discovering latent topic representations. However, existing RTMs have limitations in both the restricted model expressiveness and incapability of dealing with imbalanced network data. To expand the scope and improve the inference accuracy of RTMs, this paper presents three extensions: 1) unlike the common link likelihood with a diagonal weight matrix that allows the-same-topic interactions only, we generalize it to use a full weight matrix that captures all pairwise topic interactions and is applicable to asymmetric networks; 2) instead of doing standard Bayesian inference, we perform regularized Bayesian inference (RegBayes) with a regularization parameter to deal with the imbalanced link structure issue in real networks and improve the discriminative ability of learned latent representations; and 3) instead of doing variational approximation with strict mean-field assumptions, we present collapsed Gibbs sampling algorithms for the generalized relational topic models by exploring data augmentation without making restricting assumptions. Under the generic RegBayes framework, we carefully investigate two popular discriminative loss functions, namely, the logistic log-loss and the max-margin hinge loss. Experimental results on several real network datasets demonstrate the significance of these extensions on improving prediction performance.
A New Modified Histogram Matching Normalization for Time Series Microarray Analysis

PubMed Central

Astola, Laura; Molenaar, Jaap

2014-01-01

Microarray data is often utilized in inferring regulatory networks. Quantile normalization (QN) is a popular method to reduce array-to-array variation. We show that in the context of time series measurements QN may not be the best choice for this task, especially not if the inference is based on continuous time ODE model. We propose an alternative normalization method that is better suited for network inference from time series data. PMID:27600344
Causal inference in biology networks with integrated belief propagation.

PubMed

Chang, Rui; Karr, Jonathan R; Schadt, Eric E

2015-01-01

Inferring causal relationships among molecular and higher order phenotypes is a critical step in elucidating the complexity of living systems. Here we propose a novel method for inferring causality that is no longer constrained by the conditional dependency arguments that limit the ability of statistical causal inference methods to resolve causal relationships within sets of graphical models that are Markov equivalent. Our method utilizes Bayesian belief propagation to infer the responses of perturbation events on molecular traits given a hypothesized graph structure. A distance measure between the inferred response distribution and the observed data is defined to assess the 'fitness' of the hypothesized causal relationships. To test our algorithm, we infer causal relationships within equivalence classes of gene networks in which the form of the functional interactions that are possible are assumed to be nonlinear, given synthetic microarray and RNA sequencing data. We also apply our method to infer causality in real metabolic network with v-structure and feedback loop. We show that our method can recapitulate the causal structure and recover the feedback loop only from steady-state data which conventional method cannot.
Reasoning and Knowledge Acquisition Framework for 5G Network Analytics

PubMed Central

2017-01-01

Autonomic self-management is a key challenge for next-generation networks. This paper proposes an automated analysis framework to infer knowledge in 5G networks with the aim to understand the network status and to predict potential situations that might disrupt the network operability. The framework is based on the Endsley situational awareness model, and integrates automated capabilities for metrics discovery, pattern recognition, prediction techniques and rule-based reasoning to infer anomalous situations in the current operational context. Those situations should then be mitigated, either proactive or reactively, by a more complex decision-making process. The framework is driven by a use case methodology, where the network administrator is able to customize the knowledge inference rules and operational parameters. The proposal has also been instantiated to prove its adaptability to a real use case. To this end, a reference network traffic dataset was used to identify suspicious patterns and to predict the behavior of the monitored data volume. The preliminary results suggest a good level of accuracy on the inference of anomalous traffic volumes based on a simple configuration. PMID:29065473
Reasoning and Knowledge Acquisition Framework for 5G Network Analytics.

PubMed

Sotelo Monge, Marco Antonio; Maestre Vidal, Jorge; García Villalba, Luis Javier

2017-10-21

Autonomic self-management is a key challenge for next-generation networks. This paper proposes an automated analysis framework to infer knowledge in 5G networks with the aim to understand the network status and to predict potential situations that might disrupt the network operability. The framework is based on the Endsley situational awareness model, and integrates automated capabilities for metrics discovery, pattern recognition, prediction techniques and rule-based reasoning to infer anomalous situations in the current operational context. Those situations should then be mitigated, either proactive or reactively, by a more complex decision-making process. The framework is driven by a use case methodology, where the network administrator is able to customize the knowledge inference rules and operational parameters. The proposal has also been instantiated to prove its adaptability to a real use case. To this end, a reference network traffic dataset was used to identify suspicious patterns and to predict the behavior of the monitored data volume. The preliminary results suggest a good level of accuracy on the inference of anomalous traffic volumes based on a simple configuration.
Semi-Supervised Multi-View Learning for Gene Network Reconstruction

PubMed Central

Ceci, Michelangelo; Pio, Gianvito; Kuzmanovski, Vladimir; Džeroski, Sašo

2015-01-01

The task of gene regulatory network reconstruction from high-throughput data is receiving increasing attention in recent years. As a consequence, many inference methods for solving this task have been proposed in the literature. It has been recently observed, however, that no single inference method performs optimally across all datasets. It has also been shown that the integration of predictions from multiple inference methods is more robust and shows high performance across diverse datasets. Inspired by this research, in this paper, we propose a machine learning solution which learns to combine predictions from multiple inference methods. While this approach adds additional complexity to the inference process, we expect it would also carry substantial benefits. These would come from the automatic adaptation to patterns on the outputs of individual inference methods, so that it is possible to identify regulatory interactions more reliably when these patterns occur. This article demonstrates the benefits (in terms of accuracy of the reconstructed networks) of the proposed method, which exploits an iterative, semi-supervised ensemble-based algorithm. The algorithm learns to combine the interactions predicted by many different inference methods in the multi-view learning setting. The empirical evaluation of the proposed algorithm on a prokaryotic model organism (E. coli) and on a eukaryotic model organism (S. cerevisiae) clearly shows improved performance over the state of the art methods. The results indicate that gene regulatory network reconstruction for the real datasets is more difficult for S. cerevisiae than for E. coli. The software, all the datasets used in the experiments and all the results are available for download at the following link: http://figshare.com/articles/Semi_supervised_Multi_View_Learning_for_Gene_Network_Reconstruction/1604827. PMID:26641091
Usefulness of Neuro-Fuzzy Models' Application for Tobacco Control

NASA Astrophysics Data System (ADS)

Petrovic-Lazarevic, Sonja; Zhang, Jian Ying

2007-12-01

The paper presents neuro-fuzzy models' application appropriate for tobacco control: the fuzzy control model, Adaptive Network Based Fuzzy Inference System, Evolving Fuzzy Neural Network models, and EVOlving POLicies. We propose further the use of Fuzzy Casual Networks to help tobacco control decision makers develop policies and measure their impact on social regulation.
Enhancing gene regulatory network inference through data integration with markov random fields

DOE PAGES

Banf, Michael; Rhee, Seung Y.

2017-02-01

Here, a gene regulatory network links transcription factors to their target genes and represents a map of transcriptional regulation. Much progress has been made in deciphering gene regulatory networks computationally. However, gene regulatory network inference for most eukaryotic organisms remain challenging. To improve the accuracy of gene regulatory network inference and facilitate candidate selection for experimentation, we developed an algorithm called GRACE (Gene Regulatory network inference ACcuracy Enhancement). GRACE exploits biological a priori and heterogeneous data integration to generate high- confidence network predictions for eukaryotic organisms using Markov Random Fields in a semi-supervised fashion. GRACE uses a novel optimization schememore » to integrate regulatory evidence and biological relevance. It is particularly suited for model learning with sparse regulatory gold standard data. We show GRACE’s potential to produce high confidence regulatory networks compared to state of the art approaches using Drosophila melanogaster and Arabidopsis thaliana data. In an A. thaliana developmental gene regulatory network, GRACE recovers cell cycle related regulatory mechanisms and further hypothesizes several novel regulatory links, including a putative control mechanism of vascular structure formation due to modifications in cell proliferation.« less
Enhancing gene regulatory network inference through data integration with markov random fields

DOE Office of Scientific and Technical Information (OSTI.GOV)

Banf, Michael; Rhee, Seung Y.

Here, a gene regulatory network links transcription factors to their target genes and represents a map of transcriptional regulation. Much progress has been made in deciphering gene regulatory networks computationally. However, gene regulatory network inference for most eukaryotic organisms remain challenging. To improve the accuracy of gene regulatory network inference and facilitate candidate selection for experimentation, we developed an algorithm called GRACE (Gene Regulatory network inference ACcuracy Enhancement). GRACE exploits biological a priori and heterogeneous data integration to generate high- confidence network predictions for eukaryotic organisms using Markov Random Fields in a semi-supervised fashion. GRACE uses a novel optimization schememore » to integrate regulatory evidence and biological relevance. It is particularly suited for model learning with sparse regulatory gold standard data. We show GRACE’s potential to produce high confidence regulatory networks compared to state of the art approaches using Drosophila melanogaster and Arabidopsis thaliana data. In an A. thaliana developmental gene regulatory network, GRACE recovers cell cycle related regulatory mechanisms and further hypothesizes several novel regulatory links, including a putative control mechanism of vascular structure formation due to modifications in cell proliferation.« less
Clustering network layers with the strata multilayer stochastic block model

PubMed Central

Stanley, Natalie; Shai, Saray; Taylor, Dane; Mucha, Peter J.

2016-01-01

Multilayer networks are a useful data structure for simultaneously capturing multiple types of relationships between a set of nodes. In such networks, each relational definition gives rise to a layer. While each layer provides its own set of information, community structure across layers can be collectively utilized to discover and quantify underlying relational patterns between nodes. To concisely extract information from a multilayer network, we propose to identify and combine sets of layers with meaningful similarities in community structure. In this paper, we describe the “strata multilayer stochastic block model” (sMLSBM), a probabilistic model for multilayer community structure. The central extension of the model is that there exist groups of layers, called “strata”, which are defined such that all layers in a given stratum have community structure described by a common stochastic block model (SBM). That is, layers in a stratum exhibit similar node-to-community assignments and SBM probability parameters. Fitting the sMLSBM to a multilayer network provides a joint clustering that yields node-to-community and layer-to-stratum assignments, which cooperatively aid one another during inference. We describe an algorithm for separating layers into their appropriate strata and an inference technique for estimating the SBM parameters for each stratum. We demonstrate our method using synthetic networks and a multilayer network inferred from data collected in the Human Microbiome Project. PMID:28435844
Random graph models for dynamic networks

NASA Astrophysics Data System (ADS)

Zhang, Xiao; Moore, Cristopher; Newman, Mark E. J.

2017-10-01

Recent theoretical work on the modeling of network structure has focused primarily on networks that are static and unchanging, but many real-world networks change their structure over time. There exist natural generalizations to the dynamic case of many static network models, including the classic random graph, the configuration model, and the stochastic block model, where one assumes that the appearance and disappearance of edges are governed by continuous-time Markov processes with rate parameters that can depend on properties of the nodes. Here we give an introduction to this class of models, showing for instance how one can compute their equilibrium properties. We also demonstrate their use in data analysis and statistical inference, giving efficient algorithms for fitting them to observed network data using the method of maximum likelihood. This allows us, for example, to estimate the time constants of network evolution or infer community structure from temporal network data using cues embedded both in the probabilities over time that node pairs are connected by edges and in the characteristic dynamics of edge appearance and disappearance. We illustrate these methods with a selection of applications, both to computer-generated test networks and real-world examples.
Knowledge-guided fuzzy logic modeling to infer cellular signaling networks from proteomic data

PubMed Central

Liu, Hui; Zhang, Fan; Mishra, Shital Kumar; Zhou, Shuigeng; Zheng, Jie

2016-01-01

Modeling of signaling pathways is crucial for understanding and predicting cellular responses to drug treatments. However, canonical signaling pathways curated from literature are seldom context-specific and thus can hardly predict cell type-specific response to external perturbations; purely data-driven methods also have drawbacks such as limited biological interpretability. Therefore, hybrid methods that can integrate prior knowledge and real data for network inference are highly desirable. In this paper, we propose a knowledge-guided fuzzy logic network model to infer signaling pathways by exploiting both prior knowledge and time-series data. In particular, the dynamic time warping algorithm is employed to measure the goodness of fit between experimental and predicted data, so that our method can model temporally-ordered experimental observations. We evaluated the proposed method on a synthetic dataset and two real phosphoproteomic datasets. The experimental results demonstrate that our model can uncover drug-induced alterations in signaling pathways in cancer cells. Compared with existing hybrid models, our method can model feedback loops so that the dynamical mechanisms of signaling networks can be uncovered from time-series data. By calibrating generic models of signaling pathways against real data, our method supports precise predictions of context-specific anticancer drug effects, which is an important step towards precision medicine. PMID:27774993
Representing Micro-Macro Linkages by Actor-Based Dynamic Network Models

ERIC Educational Resources Information Center

Snijders, Tom A. B.; Steglich, Christian E. G.

2015-01-01

Stochastic actor-based models for network dynamics have the primary aim of statistical inference about processes of network change, but may be regarded as a kind of agent-based models. Similar to many other agent-based models, they are based on local rules for actor behavior. Different from many other agent-based models, by including elements of…
Evaluation of artificial time series microarray data for dynamic gene regulatory network inference.

PubMed

Xenitidis, P; Seimenis, I; Kakolyris, S; Adamopoulos, A

2017-08-07

High-throughput technology like microarrays is widely used in the inference of gene regulatory networks (GRNs). We focused on time series data since we are interested in the dynamics of GRNs and the identification of dynamic networks. We evaluated the amount of information that exists in artificial time series microarray data and the ability of an inference process to produce accurate models based on them. We used dynamic artificial gene regulatory networks in order to create artificial microarray data. Key features that characterize microarray data such as the time separation of directly triggered genes, the percentage of directly triggered genes and the triggering function type were altered in order to reveal the limits that are imposed by the nature of microarray data on the inference process. We examined the effect of various factors on the inference performance such as the network size, the presence of noise in microarray data, and the network sparseness. We used a system theory approach and examined the relationship between the pole placement of the inferred system and the inference performance. We examined the relationship between the inference performance in the time domain and the true system parameter identification. Simulation results indicated that time separation and the percentage of directly triggered genes are crucial factors. Also, network sparseness, the triggering function type and noise in input data affect the inference performance. When two factors were simultaneously varied, it was found that variation of one parameter significantly affects the dynamic response of the other. Crucial factors were also examined using a real GRN and acquired results confirmed simulation findings with artificial data. Different initial conditions were also used as an alternative triggering approach. Relevant results confirmed that the number of datasets constitutes the most significant parameter with regard to the inference performance. Copyright © 2017 Elsevier Ltd. All rights reserved.
A generative model of whole-brain effective connectivity.

PubMed

Frässle, Stefan; Lomakina, Ekaterina I; Kasper, Lars; Manjaly, Zina M; Leff, Alex; Pruessmann, Klaas P; Buhmann, Joachim M; Stephan, Klaas E

2018-05-25

The development of whole-brain models that can infer effective (directed) connection strengths from fMRI data represents a central challenge for computational neuroimaging. A recently introduced generative model of fMRI data, regression dynamic causal modeling (rDCM), moves towards this goal as it scales gracefully to very large networks. However, large-scale networks with thousands of connections are difficult to interpret; additionally, one typically lacks information (data points per free parameter) for precise estimation of all model parameters. This paper introduces sparsity constraints to the variational Bayesian framework of rDCM as a solution to these problems in the domain of task-based fMRI. This sparse rDCM approach enables highly efficient effective connectivity analyses in whole-brain networks and does not require a priori assumptions about the network's connectivity structure but prunes fully (all-to-all) connected networks as part of model inversion. Following the derivation of the variational Bayesian update equations for sparse rDCM, we use both simulated and empirical data to assess the face validity of the model. In particular, we show that it is feasible to infer effective connection strengths from fMRI data using a network with more than 100 regions and 10,000 connections. This demonstrates the feasibility of whole-brain inference on effective connectivity from fMRI data - in single subjects and with a run-time below 1 min when using parallelized code. We anticipate that sparse rDCM may find useful application in connectomics and clinical neuromodeling - for example, for phenotyping individual patients in terms of whole-brain network structure. Copyright © 2018. Published by Elsevier Inc.
GRN2SBML: automated encoding and annotation of inferred gene regulatory networks complying with SBML.

PubMed

Vlaic, Sebastian; Hoffmann, Bianca; Kupfer, Peter; Weber, Michael; Dräger, Andreas

2013-09-01

GRN2SBML automatically encodes gene regulatory networks derived from several inference tools in systems biology markup language. Providing a graphical user interface, the networks can be annotated via the simple object access protocol (SOAP)-based application programming interface of BioMart Central Portal and minimum information required in the annotation of models registry. Additionally, we provide an R-package, which processes the output of supported inference algorithms and automatically passes all required parameters to GRN2SBML. Therefore, GRN2SBML closes a gap in the processing pipeline between the inference of gene regulatory networks and their subsequent analysis, visualization and storage. GRN2SBML is freely available under the GNU Public License version 3 and can be downloaded from http://www.hki-jena.de/index.php/0/2/490. General information on GRN2SBML, examples and tutorials are available at the tool's web page.
A novel gene network inference algorithm using predictive minimum description length approach.

PubMed

Chaitankar, Vijender; Ghosh, Preetam; Perkins, Edward J; Gong, Ping; Deng, Youping; Zhang, Chaoyang

2010-05-28

Reverse engineering of gene regulatory networks using information theory models has received much attention due to its simplicity, low computational cost, and capability of inferring large networks. One of the major problems with information theory models is to determine the threshold which defines the regulatory relationships between genes. The minimum description length (MDL) principle has been implemented to overcome this problem. The description length of the MDL principle is the sum of model length and data encoding length. A user-specified fine tuning parameter is used as control mechanism between model and data encoding, but it is difficult to find the optimal parameter. In this work, we proposed a new inference algorithm which incorporated mutual information (MI), conditional mutual information (CMI) and predictive minimum description length (PMDL) principle to infer gene regulatory networks from DNA microarray data. In this algorithm, the information theoretic quantities MI and CMI determine the regulatory relationships between genes and the PMDL principle method attempts to determine the best MI threshold without the need of a user-specified fine tuning parameter. The performance of the proposed algorithm was evaluated using both synthetic time series data sets and a biological time series data set for the yeast Saccharomyces cerevisiae. The benchmark quantities precision and recall were used as performance measures. The results show that the proposed algorithm produced less false edges and significantly improved the precision, as compared to the existing algorithm. For further analysis the performance of the algorithms was observed over different sizes of data. We have proposed a new algorithm that implements the PMDL principle for inferring gene regulatory networks from time series DNA microarray data that eliminates the need of a fine tuning parameter. The evaluation results obtained from both synthetic and actual biological data sets show that the PMDL principle is effective in determining the MI threshold and the developed algorithm improves precision of gene regulatory network inference. Based on the sensitivity analysis of all tested cases, an optimal CMI threshold value has been identified. Finally it was observed that the performance of the algorithms saturates at a certain threshold of data size.

Process-driven inference of biological network structure: feasibility, minimality, and multiplicity

NASA Astrophysics Data System (ADS)

Zeng, Chen

2012-02-01

For a given dynamic process, identifying the putative interaction networks to achieve it is the inference problem. In this talk, we address the computational complexity of inference problem in the context of Boolean networks under dominant inhibition condition. The first is a proof that the feasibility problem (is there a network that explains the dynamics?) can be solved in polynomial-time. Second, while the minimality problem (what is the smallest network that explains the dynamics?) is shown to be NP-hard, a simple polynomial-time heuristic is shown to produce near-minimal solutions, as demonstrated by simulation. Third, the theoretical framework also leads to a fast polynomial-time heuristic to estimate the number of network solutions with reasonable accuracy. We will apply these approaches to two simplified Boolean network models for the cell cycle process of budding yeast (Li 2004) and fission yeast (Davidich 2008). Our results demonstrate that each of these networks contains a giant backbone motif spanning all the network nodes that provides the desired main functionality, while the remaining edges in the network form smaller motifs whose role is to confer stability properties rather than provide function. Moreover, we show that the bioprocesses of these two cell cycle models differ considerably from a typically generated process and are intrinsically cascade-like.
Predictive minimum description length principle approach to inferring gene regulatory networks.

PubMed

Chaitankar, Vijender; Zhang, Chaoyang; Ghosh, Preetam; Gong, Ping; Perkins, Edward J; Deng, Youping

2011-01-01

Reverse engineering of gene regulatory networks using information theory models has received much attention due to its simplicity, low computational cost, and capability of inferring large networks. One of the major problems with information theory models is to determine the threshold that defines the regulatory relationships between genes. The minimum description length (MDL) principle has been implemented to overcome this problem. The description length of the MDL principle is the sum of model length and data encoding length. A user-specified fine tuning parameter is used as control mechanism between model and data encoding, but it is difficult to find the optimal parameter. In this work, we propose a new inference algorithm that incorporates mutual information (MI), conditional mutual information (CMI), and predictive minimum description length (PMDL) principle to infer gene regulatory networks from DNA microarray data. In this algorithm, the information theoretic quantities MI and CMI determine the regulatory relationships between genes and the PMDL principle method attempts to determine the best MI threshold without the need of a user-specified fine tuning parameter. The performance of the proposed algorithm is evaluated using both synthetic time series data sets and a biological time series data set (Saccharomyces cerevisiae). The results show that the proposed algorithm produced fewer false edges and significantly improved the precision when compared to existing MDL algorithm.
Diurnal Transcriptome and Gene Network Represented through Sparse Modeling in Brachypodium distachyon.

PubMed

Koda, Satoru; Onda, Yoshihiko; Matsui, Hidetoshi; Takahagi, Kotaro; Yamaguchi-Uehara, Yukiko; Shimizu, Minami; Inoue, Komaki; Yoshida, Takuhiro; Sakurai, Tetsuya; Honda, Hiroshi; Eguchi, Shinto; Nishii, Ryuei; Mochida, Keiichi

2017-01-01

We report the comprehensive identification of periodic genes and their network inference, based on a gene co-expression analysis and an Auto-Regressive eXogenous (ARX) model with a group smoothly clipped absolute deviation (SCAD) method using a time-series transcriptome dataset in a model grass, Brachypodium distachyon . To reveal the diurnal changes in the transcriptome in B. distachyon , we performed RNA-seq analysis of its leaves sampled through a diurnal cycle of over 48 h at 4 h intervals using three biological replications, and identified 3,621 periodic genes through our wavelet analysis. The expression data are feasible to infer network sparsity based on ARX models. We found that genes involved in biological processes such as transcriptional regulation, protein degradation, and post-transcriptional modification and photosynthesis are significantly enriched in the periodic genes, suggesting that these processes might be regulated by circadian rhythm in B. distachyon . On the basis of the time-series expression patterns of the periodic genes, we constructed a chronological gene co-expression network and identified putative transcription factors encoding genes that might be involved in the time-specific regulatory transcriptional network. Moreover, we inferred a transcriptional network composed of the periodic genes in B. distachyon , aiming to identify genes associated with other genes through variable selection by grouping time points for each gene. Based on the ARX model with the group SCAD regularization using our time-series expression datasets of the periodic genes, we constructed gene networks and found that the networks represent typical scale-free structure. Our findings demonstrate that the diurnal changes in the transcriptome in B. distachyon leaves have a sparse network structure, demonstrating the spatiotemporal gene regulatory network over the cyclic phase transitions in B. distachyon diurnal growth.
Nonparametric weighted stochastic block models

NASA Astrophysics Data System (ADS)

Peixoto, Tiago P.

2018-01-01

We present a Bayesian formulation of weighted stochastic block models that can be used to infer the large-scale modular structure of weighted networks, including their hierarchical organization. Our method is nonparametric, and thus does not require the prior knowledge of the number of groups or other dimensions of the model, which are instead inferred from data. We give a comprehensive treatment of different kinds of edge weights (i.e., continuous or discrete, signed or unsigned, bounded or unbounded), as well as arbitrary weight transformations, and describe an unsupervised model selection approach to choose the best network description. We illustrate the application of our method to a variety of empirical weighted networks, such as global migrations, voting patterns in congress, and neural connections in the human brain.
Statistical inference, the bootstrap, and neural-network modeling with application to foreign exchange rates.

PubMed

White, H; Racine, J

2001-01-01

We propose tests for individual and joint irrelevance of network inputs. Such tests can be used to determine whether an input or group of inputs "belong" in a particular model, thus permitting valid statistical inference based on estimated feedforward neural-network models. The approaches employ well-known statistical resampling techniques. We conduct a small Monte Carlo experiment showing that our tests have reasonable level and power behavior, and we apply our methods to examine whether there are predictable regularities in foreign exchange rates. We find that exchange rates do appear to contain information that is exploitable for enhanced point prediction, but the nature of the predictive relations evolves through time.
Personalized recommendation via an improved NBI algorithm and user influence model in a Microblog network

NASA Astrophysics Data System (ADS)

Lian, Jie; Liu, Yun; Zhang, Zhen-jiang; Gui, Chang-ni

2013-10-01

Bipartite network based recommendations have attracted extensive attentions in recent years. Differing from traditional object-oriented recommendations, the recommendation in a Microblog network has two crucial differences. One is high authority users or one’s special friends usually play a very active role in tweet-oriented recommendation. The other is that the object in a Microblog network corresponds to a set of tweets on same topic instead of an actual and single entity, e.g. goods or movies in traditional networks. Thus repeat recommendations of the tweets in one’s collected topics are indispensable. Therefore, this paper improves network based inference (NBI) algorithm by original link matrix and link weight on resource allocation processes. This paper finally proposes the Microblog recommendation model based on the factors of improved network based inference and user influence model. Adjusting the weights of these two factors could generate the best recommendation results in algorithm accuracy and recommendation personalization.
Predictive regulatory models in Drosophila melanogaster by integrative inference of transcriptional networks

PubMed Central

Marbach, Daniel; Roy, Sushmita; Ay, Ferhat; Meyer, Patrick E.; Candeias, Rogerio; Kahveci, Tamer; Bristow, Christopher A.; Kellis, Manolis

2012-01-01

Gaining insights on gene regulation from large-scale functional data sets is a grand challenge in systems biology. In this article, we develop and apply methods for transcriptional regulatory network inference from diverse functional genomics data sets and demonstrate their value for gene function and gene expression prediction. We formulate the network inference problem in a machine-learning framework and use both supervised and unsupervised methods to predict regulatory edges by integrating transcription factor (TF) binding, evolutionarily conserved sequence motifs, gene expression, and chromatin modification data sets as input features. Applying these methods to Drosophila melanogaster, we predict ∼300,000 regulatory edges in a network of ∼600 TFs and 12,000 target genes. We validate our predictions using known regulatory interactions, gene functional annotations, tissue-specific expression, protein–protein interactions, and three-dimensional maps of chromosome conformation. We use the inferred network to identify putative functions for hundreds of previously uncharacterized genes, including many in nervous system development, which are independently confirmed based on their tissue-specific expression patterns. Last, we use the regulatory network to predict target gene expression levels as a function of TF expression, and find significantly higher predictive power for integrative networks than for motif or ChIP-based networks. Our work reveals the complementarity between physical evidence of regulatory interactions (TF binding, motif conservation) and functional evidence (coordinated expression or chromatin patterns) and demonstrates the power of data integration for network inference and studies of gene regulation at the systems level. PMID:22456606
Dynamic Network-Based Epistasis Analysis: Boolean Examples

PubMed Central

Azpeitia, Eugenio; Benítez, Mariana; Padilla-Longoria, Pablo; Espinosa-Soto, Carlos; Alvarez-Buylla, Elena R.

2011-01-01

In this article we focus on how the hierarchical and single-path assumptions of epistasis analysis can bias the inference of gene regulatory networks. Here we emphasize the critical importance of dynamic analyses, and specifically illustrate the use of Boolean network models. Epistasis in a broad sense refers to gene interactions, however, as originally proposed by Bateson, epistasis is defined as the blocking of a particular allelic effect due to the effect of another allele at a different locus (herein, classical epistasis). Classical epistasis analysis has proven powerful and useful, allowing researchers to infer and assign directionality to gene interactions. As larger data sets are becoming available, the analysis of classical epistasis is being complemented with computer science tools and system biology approaches. We show that when the hierarchical and single-path assumptions are not met in classical epistasis analysis, the access to relevant information and the correct inference of gene interaction topologies is hindered, and it becomes necessary to consider the temporal dynamics of gene interactions. The use of dynamical networks can overcome these limitations. We particularly focus on the use of Boolean networks that, like classical epistasis analysis, relies on logical formalisms, and hence can complement classical epistasis analysis and relax its assumptions. We develop a couple of theoretical examples and analyze them from a dynamic Boolean network model perspective. Boolean networks could help to guide additional experiments and discern among alternative regulatory schemes that would be impossible or difficult to infer without the elimination of these assumption from the classical epistasis analysis. We also use examples from the literature to show how a Boolean network-based approach has resolved ambiguities and guided epistasis analysis. Our article complements previous accounts, not only by focusing on the implications of the hierarchical and single-path assumption, but also by demonstrating the importance of considering temporal dynamics, and specifically introducing the usefulness of Boolean network models and also reviewing some key properties of network approaches. PMID:22645556
Evaluating methods of inferring gene regulatory networks highlights their lack of performance for single cell gene expression data.

PubMed

Chen, Shuonan; Mar, Jessica C

2018-06-19

A fundamental fact in biology states that genes do not operate in isolation, and yet, methods that infer regulatory networks for single cell gene expression data have been slow to emerge. With single cell sequencing methods now becoming accessible, general network inference algorithms that were initially developed for data collected from bulk samples may not be suitable for single cells. Meanwhile, although methods that are specific for single cell data are now emerging, whether they have improved performance over general methods is unknown. In this study, we evaluate the applicability of five general methods and three single cell methods for inferring gene regulatory networks from both experimental single cell gene expression data and in silico simulated data. Standard evaluation metrics using ROC curves and Precision-Recall curves against reference sets sourced from the literature demonstrated that most of the methods performed poorly when they were applied to either experimental single cell data, or simulated single cell data, which demonstrates their lack of performance for this task. Using default settings, network methods were applied to the same datasets. Comparisons of the learned networks highlighted the uniqueness of some predicted edges for each method. The fact that different methods infer networks that vary substantially reflects the underlying mathematical rationale and assumptions that distinguish network methods from each other. This study provides a comprehensive evaluation of network modeling algorithms applied to experimental single cell gene expression data and in silico simulated datasets where the network structure is known. Comparisons demonstrate that most of these assessed network methods are not able to predict network structures from single cell expression data accurately, even if they are specifically developed for single cell methods. Also, single cell methods, which usually depend on more elaborative algorithms, in general have less similarity to each other in the sets of edges detected. The results from this study emphasize the importance for developing more accurate optimized network modeling methods that are compatible for single cell data. Newly-developed single cell methods may uniquely capture particular features of potential gene-gene relationships, and caution should be taken when we interpret these results.
Predicting gene regulatory networks by combining spatial and temporal gene expression data in Arabidopsis root stem cells

PubMed Central

de Luis Balaguer, Maria Angels; Fisher, Adam P.; Clark, Natalie M.; Fernandez-Espinosa, Maria Guadalupe; Möller, Barbara K.; Weijers, Dolf; Williams, Cranos; Lorenzo, Oscar; Sozzani, Rosangela

2017-01-01

Identifying the transcription factors (TFs) and associated networks involved in stem cell regulation is essential for understanding the initiation and growth of plant tissues and organs. Although many TFs have been shown to have a role in the Arabidopsis root stem cells, a comprehensive view of the transcriptional signature of the stem cells is lacking. In this work, we used spatial and temporal transcriptomic data to predict interactions among the genes involved in stem cell regulation. To accomplish this, we transcriptionally profiled several stem cell populations and developed a gene regulatory network inference algorithm that combines clustering with dynamic Bayesian network inference. We leveraged the topology of our networks to infer potential major regulators. Specifically, through mathematical modeling and experimental validation, we identified PERIANTHIA (PAN) as an important molecular regulator of quiescent center function. The results presented in this work show that our combination of molecular biology, computational biology, and mathematical modeling is an efficient approach to identify candidate factors that function in the stem cells. PMID:28827319
Reconstruction of stochastic temporal networks through diffusive arrival times

NASA Astrophysics Data System (ADS)

Li, Xun; Li, Xiang

2017-06-01

Temporal networks have opened a new dimension in defining and quantification of complex interacting systems. Our ability to identify and reproduce time-resolved interaction patterns is, however, limited by the restricted access to empirical individual-level data. Here we propose an inverse modelling method based on first-arrival observations of the diffusion process taking place on temporal networks. We describe an efficient coordinate-ascent implementation for inferring stochastic temporal networks that builds in particular but not exclusively on the null model assumption of mutually independent interaction sequences at the dyadic level. The results of benchmark tests applied on both synthesized and empirical network data sets confirm the validity of our algorithm, showing the feasibility of statistically accurate inference of temporal networks only from moderate-sized samples of diffusion cascades. Our approach provides an effective and flexible scheme for the temporally augmented inverse problems of network reconstruction and has potential in a broad variety of applications.
Reconstruction of stochastic temporal networks through diffusive arrival times

PubMed Central

Li, Xun; Li, Xiang

2017-01-01

Temporal networks have opened a new dimension in defining and quantification of complex interacting systems. Our ability to identify and reproduce time-resolved interaction patterns is, however, limited by the restricted access to empirical individual-level data. Here we propose an inverse modelling method based on first-arrival observations of the diffusion process taking place on temporal networks. We describe an efficient coordinate-ascent implementation for inferring stochastic temporal networks that builds in particular but not exclusively on the null model assumption of mutually independent interaction sequences at the dyadic level. The results of benchmark tests applied on both synthesized and empirical network data sets confirm the validity of our algorithm, showing the feasibility of statistically accurate inference of temporal networks only from moderate-sized samples of diffusion cascades. Our approach provides an effective and flexible scheme for the temporally augmented inverse problems of network reconstruction and has potential in a broad variety of applications. PMID:28604687
Recursive regularization for inferring gene networks from time-course gene expression profiles

PubMed Central

Shimamura, Teppei; Imoto, Seiya; Yamaguchi, Rui; Fujita, André; Nagasaki, Masao; Miyano, Satoru

2009-01-01

Background Inferring gene networks from time-course microarray experiments with vector autoregressive (VAR) model is the process of identifying functional associations between genes through multivariate time series. This problem can be cast as a variable selection problem in Statistics. One of the promising methods for variable selection is the elastic net proposed by Zou and Hastie (2005). However, VAR modeling with the elastic net succeeds in increasing the number of true positives while it also results in increasing the number of false positives. Results By incorporating relative importance of the VAR coefficients into the elastic net, we propose a new class of regularization, called recursive elastic net, to increase the capability of the elastic net and estimate gene networks based on the VAR model. The recursive elastic net can reduce the number of false positives gradually by updating the importance. Numerical simulations and comparisons demonstrate that the proposed method succeeds in reducing the number of false positives drastically while keeping the high number of true positives in the network inference and achieves two or more times higher true discovery rate (the proportion of true positives among the selected edges) than the competing methods even when the number of time points is small. We also compared our method with various reverse-engineering algorithms on experimental data of MCF-7 breast cancer cells stimulated with two ErbB ligands, EGF and HRG. Conclusion The recursive elastic net is a powerful tool for inferring gene networks from time-course gene expression profiles. PMID:19386091
Inferring dynamic gene regulatory networks in cardiac differentiation through the integration of multi-dimensional data.

PubMed

Gong, Wuming; Koyano-Nakagawa, Naoko; Li, Tongbin; Garry, Daniel J

2015-03-07

Decoding the temporal control of gene expression patterns is key to the understanding of the complex mechanisms that govern developmental decisions during heart development. High-throughput methods have been employed to systematically study the dynamic and coordinated nature of cardiac differentiation at the global level with multiple dimensions. Therefore, there is a pressing need to develop a systems approach to integrate these data from individual studies and infer the dynamic regulatory networks in an unbiased fashion. We developed a two-step strategy to integrate data from (1) temporal RNA-seq, (2) temporal histone modification ChIP-seq, (3) transcription factor (TF) ChIP-seq and (4) gene perturbation experiments to reconstruct the dynamic network during heart development. First, we trained a logistic regression model to predict the probability (LR score) of any base being bound by 543 TFs with known positional weight matrices. Second, four dimensions of data were combined using a time-varying dynamic Bayesian network model to infer the dynamic networks at four developmental stages in the mouse [mouse embryonic stem cells (ESCs), mesoderm (MES), cardiac progenitors (CP) and cardiomyocytes (CM)]. Our method not only infers the time-varying networks between different stages of heart development, but it also identifies the TF binding sites associated with promoter or enhancers of downstream genes. The LR scores of experimentally verified ESCs and heart enhancers were significantly higher than random regions (p <10(-100)), suggesting that a high LR score is a reliable indicator for functional TF binding sites. Our network inference model identified a region with an elevated LR score approximately -9400 bp upstream of the transcriptional start site of Nkx2-5, which overlapped with a previously reported enhancer region (-9435 to -8922 bp). TFs such as Tead1, Gata4, Msx2, and Tgif1 were predicted to bind to this region and participate in the regulation of Nkx2-5 gene expression. Our model also predicted the key regulatory networks for the ESC-MES, MES-CP and CP-CM transitions. We report a novel method to systematically integrate multi-dimensional -omics data and reconstruct the gene regulatory networks. This method will allow one to rapidly determine the cis-modules that regulate key genes during cardiac differentiation.
Linear time-varying models can reveal non-linear interactions of biomolecular regulatory networks using multiple time-series data.

PubMed

Kim, Jongrae; Bates, Declan G; Postlethwaite, Ian; Heslop-Harrison, Pat; Cho, Kwang-Hyun

2008-05-15

Inherent non-linearities in biomolecular interactions make the identification of network interactions difficult. One of the principal problems is that all methods based on the use of linear time-invariant models will have fundamental limitations in their capability to infer certain non-linear network interactions. Another difficulty is the multiplicity of possible solutions, since, for a given dataset, there may be many different possible networks which generate the same time-series expression profiles. A novel algorithm for the inference of biomolecular interaction networks from temporal expression data is presented. Linear time-varying models, which can represent a much wider class of time-series data than linear time-invariant models, are employed in the algorithm. From time-series expression profiles, the model parameters are identified by solving a non-linear optimization problem. In order to systematically reduce the set of possible solutions for the optimization problem, a filtering process is performed using a phase-portrait analysis with random numerical perturbations. The proposed approach has the advantages of not requiring the system to be in a stable steady state, of using time-series profiles which have been generated by a single experiment, and of allowing non-linear network interactions to be identified. The ability of the proposed algorithm to correctly infer network interactions is illustrated by its application to three examples: a non-linear model for cAMP oscillations in Dictyostelium discoideum, the cell-cycle data for Saccharomyces cerevisiae and a large-scale non-linear model of a group of synchronized Dictyostelium cells. The software used in this article is available from http://sbie.kaist.ac.kr/software
Gene Regulatory Network Inferences Using a Maximum-Relevance and Maximum-Significance Strategy

PubMed Central

Liu, Wei; Zhu, Wen; Liao, Bo; Chen, Xiangtao

2016-01-01

Recovering gene regulatory networks from expression data is a challenging problem in systems biology that provides valuable information on the regulatory mechanisms of cells. A number of algorithms based on computational models are currently used to recover network topology. However, most of these algorithms have limitations. For example, many models tend to be complicated because of the “large p, small n” problem. In this paper, we propose a novel regulatory network inference method called the maximum-relevance and maximum-significance network (MRMSn) method, which converts the problem of recovering networks into a problem of how to select the regulator genes for each gene. To solve the latter problem, we present an algorithm that is based on information theory and selects the regulator genes for a specific gene by maximizing the relevance and significance. A first-order incremental search algorithm is used to search for regulator genes. Eventually, a strict constraint is adopted to adjust all of the regulatory relationships according to the obtained regulator genes and thus obtain the complete network structure. We performed our method on five different datasets and compared our method to five state-of-the-art methods for network inference based on information theory. The results confirm the effectiveness of our method. PMID:27829000
Dynamic social networks based on movement

USGS Publications Warehouse

Scharf, Henry; Hooten, Mevin B.; Fosdick, Bailey K.; Johnson, Devin S.; London, Joshua M.; Durban, John W.

2016-01-01

Network modeling techniques provide a means for quantifying social structure in populations of individuals. Data used to define social connectivity are often expensive to collect and based on case-specific, ad hoc criteria. Moreover, in applications involving animal social networks, collection of these data is often opportunistic and can be invasive. Frequently, the social network of interest for a given population is closely related to the way individuals move. Thus, telemetry data, which are minimally invasive and relatively inexpensive to collect, present an alternative source of information. We develop a framework for using telemetry data to infer social relationships among animals. To achieve this, we propose a Bayesian hierarchical model with an underlying dynamic social network controlling movement of individuals via two mechanisms: an attractive effect and an aligning effect. We demonstrate the model and its ability to accurately identify complex social behavior in simulation, and apply our model to telemetry data arising from killer whales. Using auxiliary information about the study population, we investigate model validity and find the inferred dynamic social network is consistent with killer whale ecology and expert knowledge.
Inferring phenomenological models of Markov processes from data

NASA Astrophysics Data System (ADS)

Rivera, Catalina; Nemenman, Ilya

Microscopically accurate modeling of stochastic dynamics of biochemical networks is hard due to the extremely high dimensionality of the state space of such networks. Here we propose an algorithm for inference of phenomenological, coarse-grained models of Markov processes describing the network dynamics directly from data, without the intermediate step of microscopically accurate modeling. The approach relies on the linear nature of the Chemical Master Equation and uses Bayesian Model Selection for identification of parsimonious models that fit the data. When applied to synthetic data from the Kinetic Proofreading process (KPR), a common mechanism used by cells for increasing specificity of molecular assembly, the algorithm successfully uncovers the known coarse-grained description of the process. This phenomenological description has been notice previously, but this time it is derived in an automated manner by the algorithm. James S. McDonnell Foundation Grant No. 220020321.
Inferring general relations between network characteristics from specific network ensembles.

PubMed

Cardanobile, Stefano; Pernice, Volker; Deger, Moritz; Rotter, Stefan

2012-01-01

Different network models have been suggested for the topology underlying complex interactions in natural systems. These models are aimed at replicating specific statistical features encountered in real-world networks. However, it is rarely considered to which degree the results obtained for one particular network class can be extrapolated to real-world networks. We address this issue by comparing different classical and more recently developed network models with respect to their ability to generate networks with large structural variability. In particular, we consider the statistical constraints which the respective construction scheme imposes on the generated networks. After having identified the most variable networks, we address the issue of which constraints are common to all network classes and are thus suitable candidates for being generic statistical laws of complex networks. In fact, we find that generic, not model-related dependencies between different network characteristics do exist. This makes it possible to infer global features from local ones using regression models trained on networks with high generalization power. Our results confirm and extend previous findings regarding the synchronization properties of neural networks. Our method seems especially relevant for large networks, which are difficult to map completely, like the neural networks in the brain. The structure of such large networks cannot be fully sampled with the present technology. Our approach provides a method to estimate global properties of under-sampled networks in good approximation. Finally, we demonstrate on three different data sets (C. elegans neuronal network, R. prowazekii metabolic network, and a network of synonyms extracted from Roget's Thesaurus) that real-world networks have statistical relations compatible with those obtained using regression models.
Modeling of a 5-cell direct methanol fuel cell using adaptive-network-based fuzzy inference systems

NASA Astrophysics Data System (ADS)

Wang, Rongrong; Qi, Liang; Xie, Xiaofeng; Ding, Qingqing; Li, Chunwen; Ma, ChenChi M.

The methanol concentrations, temperature and current were considered as inputs, the cell voltage was taken as output, and the performance of a direct methanol fuel cell (DMFC) was modeled by adaptive-network-based fuzzy inference systems (ANFIS). The artificial neural network (ANN) and polynomial-based models were selected to be compared with the ANFIS in respect of quality and accuracy. Based on the ANFIS model obtained, the characteristics of the DMFC were studied. The results show that temperature and methanol concentration greatly affect the performance of the DMFC. Within a restricted current range, the methanol concentration does not greatly affect the stack voltage. In order to obtain higher fuel utilization efficiency, the methanol concentrations and temperatures should be adjusted according to the load on the system.

Statistical inference to advance network models in epidemiology.

PubMed

Welch, David; Bansal, Shweta; Hunter, David R

2011-03-01

Contact networks are playing an increasingly important role in the study of epidemiology. Most of the existing work in this area has focused on considering the effect of underlying network structure on epidemic dynamics by using tools from probability theory and computer simulation. This work has provided much insight on the role that heterogeneity in host contact patterns plays on infectious disease dynamics. Despite the important understanding afforded by the probability and simulation paradigm, this approach does not directly address important questions about the structure of contact networks such as what is the best network model for a particular mode of disease transmission, how parameter values of a given model should be estimated, or how precisely the data allow us to estimate these parameter values. We argue that these questions are best answered within a statistical framework and discuss the role of statistical inference in estimating contact networks from epidemiological data. Copyright © 2011 Elsevier B.V. All rights reserved.
System-level insights into the cellular interactome of a non-model organism: inferring, modelling and analysing functional gene network of soybean (Glycine max).

PubMed

Xu, Yungang; Guo, Maozu; Zou, Quan; Liu, Xiaoyan; Wang, Chunyu; Liu, Yang

2014-01-01

Cellular interactome, in which genes and/or their products interact on several levels, forming transcriptional regulatory-, protein interaction-, metabolic-, signal transduction networks, etc., has attracted decades of research focuses. However, such a specific type of network alone can hardly explain the various interactive activities among genes. These networks characterize different interaction relationships, implying their unique intrinsic properties and defects, and covering different slices of biological information. Functional gene network (FGN), a consolidated interaction network that models fuzzy and more generalized notion of gene-gene relations, have been proposed to combine heterogeneous networks with the goal of identifying functional modules supported by multiple interaction types. There are yet no successful precedents of FGNs on sparsely studied non-model organisms, such as soybean (Glycine max), due to the absence of sufficient heterogeneous interaction data. We present an alternative solution for inferring the FGNs of soybean (SoyFGNs), in a pioneering study on the soybean interactome, which is also applicable to other organisms. SoyFGNs exhibit the typical characteristics of biological networks: scale-free, small-world architecture and modularization. Verified by co-expression and KEGG pathways, SoyFGNs are more extensive and accurate than an orthology network derived from Arabidopsis. As a case study, network-guided disease-resistance gene discovery indicates that SoyFGNs can provide system-level studies on gene functions and interactions. This work suggests that inferring and modelling the interactome of a non-model plant are feasible. It will speed up the discovery and definition of the functions and interactions of other genes that control important functions, such as nitrogen fixation and protein or lipid synthesis. The efforts of the study are the basis of our further comprehensive studies on the soybean functional interactome at the genome and microRNome levels. Additionally, a web tool for information retrieval and analysis of SoyFGNs can be accessed at SoyFN: http://nclab.hit.edu.cn/SoyFN.
System-Level Insights into the Cellular Interactome of a Non-Model Organism: Inferring, Modelling and Analysing Functional Gene Network of Soybean (Glycine max)

PubMed Central

Xu, Yungang; Guo, Maozu; Zou, Quan; Liu, Xiaoyan; Wang, Chunyu; Liu, Yang

2014-01-01

Cellular interactome, in which genes and/or their products interact on several levels, forming transcriptional regulatory-, protein interaction-, metabolic-, signal transduction networks, etc., has attracted decades of research focuses. However, such a specific type of network alone can hardly explain the various interactive activities among genes. These networks characterize different interaction relationships, implying their unique intrinsic properties and defects, and covering different slices of biological information. Functional gene network (FGN), a consolidated interaction network that models fuzzy and more generalized notion of gene-gene relations, have been proposed to combine heterogeneous networks with the goal of identifying functional modules supported by multiple interaction types. There are yet no successful precedents of FGNs on sparsely studied non-model organisms, such as soybean (Glycine max), due to the absence of sufficient heterogeneous interaction data. We present an alternative solution for inferring the FGNs of soybean (SoyFGNs), in a pioneering study on the soybean interactome, which is also applicable to other organisms. SoyFGNs exhibit the typical characteristics of biological networks: scale-free, small-world architecture and modularization. Verified by co-expression and KEGG pathways, SoyFGNs are more extensive and accurate than an orthology network derived from Arabidopsis. As a case study, network-guided disease-resistance gene discovery indicates that SoyFGNs can provide system-level studies on gene functions and interactions. This work suggests that inferring and modelling the interactome of a non-model plant are feasible. It will speed up the discovery and definition of the functions and interactions of other genes that control important functions, such as nitrogen fixation and protein or lipid synthesis. The efforts of the study are the basis of our further comprehensive studies on the soybean functional interactome at the genome and microRNome levels. Additionally, a web tool for information retrieval and analysis of SoyFGNs can be accessed at SoyFN: http://nclab.hit.edu.cn/SoyFN. PMID:25423109
Microarray Data Processing Techniques for Genome-Scale Network Inference from Large Public Repositories.

PubMed

Chockalingam, Sriram; Aluru, Maneesha; Aluru, Srinivas

2016-09-19

Pre-processing of microarray data is a well-studied problem. Furthermore, all popular platforms come with their own recommended best practices for differential analysis of genes. However, for genome-scale network inference using microarray data collected from large public repositories, these methods filter out a considerable number of genes. This is primarily due to the effects of aggregating a diverse array of experiments with different technical and biological scenarios. Here we introduce a pre-processing pipeline suitable for inferring genome-scale gene networks from large microarray datasets. We show that partitioning of the available microarray datasets according to biological relevance into tissue- and process-specific categories significantly extends the limits of downstream network construction. We demonstrate the effectiveness of our pre-processing pipeline by inferring genome-scale networks for the model plant Arabidopsis thaliana using two different construction methods and a collection of 11,760 Affymetrix ATH1 microarray chips. Our pre-processing pipeline and the datasets used in this paper are made available at http://alurulab.cc.gatech.edu/microarray-pp.
Dynamics of embryonic stem cell differentiation inferred from single-cell transcriptomics show a series of transitions through discrete cell states

PubMed Central

Jang, Sumin; Choubey, Sandeep; Furchtgott, Leon; Zou, Ling-Nan; Doyle, Adele; Menon, Vilas; Loew, Ethan B; Krostag, Anne-Rachel; Martinez, Refugio A; Madisen, Linda; Levi, Boaz P; Ramanathan, Sharad

2017-01-01

The complexity of gene regulatory networks that lead multipotent cells to acquire different cell fates makes a quantitative understanding of differentiation challenging. Using a statistical framework to analyze single-cell transcriptomics data, we infer the gene expression dynamics of early mouse embryonic stem (mES) cell differentiation, uncovering discrete transitions across nine cell states. We validate the predicted transitions across discrete states using flow cytometry. Moreover, using live-cell microscopy, we show that individual cells undergo abrupt transitions from a naïve to primed pluripotent state. Using the inferred discrete cell states to build a probabilistic model for the underlying gene regulatory network, we further predict and experimentally verify that these states have unique response to perturbations, thus defining them functionally. Our study provides a framework to infer the dynamics of differentiation from single cell transcriptomics data and to build predictive models of the gene regulatory networks that drive the sequence of cell fate decisions during development. DOI: http://dx.doi.org/10.7554/eLife.20487.001 PMID:28296635
Construction of regulatory networks using expression time-series data of a genotyped population.

PubMed

Yeung, Ka Yee; Dombek, Kenneth M; Lo, Kenneth; Mittler, John E; Zhu, Jun; Schadt, Eric E; Bumgarner, Roger E; Raftery, Adrian E

2011-11-29

The inference of regulatory and biochemical networks from large-scale genomics data is a basic problem in molecular biology. The goal is to generate testable hypotheses of gene-to-gene influences and subsequently to design bench experiments to confirm these network predictions. Coexpression of genes in large-scale gene-expression data implies coregulation and potential gene-gene interactions, but provide little information about the direction of influences. Here, we use both time-series data and genetics data to infer directionality of edges in regulatory networks: time-series data contain information about the chronological order of regulatory events and genetics data allow us to map DNA variations to variations at the RNA level. We generate microarray data measuring time-dependent gene-expression levels in 95 genotyped yeast segregants subjected to a drug perturbation. We develop a Bayesian model averaging regression algorithm that incorporates external information from diverse data types to infer regulatory networks from the time-series and genetics data. Our algorithm is capable of generating feedback loops. We show that our inferred network recovers existing and novel regulatory relationships. Following network construction, we generate independent microarray data on selected deletion mutants to prospectively test network predictions. We demonstrate the potential of our network to discover de novo transcription-factor binding sites. Applying our construction method to previously published data demonstrates that our method is competitive with leading network construction algorithms in the literature.
Integrative approach for inference of gene regulatory networks using lasso-based random featuring and application to psychiatric disorders.

PubMed

Kim, Dongchul; Kang, Mingon; Biswas, Ashis; Liu, Chunyu; Gao, Jean

2016-08-10

Inferring gene regulatory networks is one of the most interesting research areas in the systems biology. Many inference methods have been developed by using a variety of computational models and approaches. However, there are two issues to solve. First, depending on the structural or computational model of inference method, the results tend to be inconsistent due to innately different advantages and limitations of the methods. Therefore the combination of dissimilar approaches is demanded as an alternative way in order to overcome the limitations of standalone methods through complementary integration. Second, sparse linear regression that is penalized by the regularization parameter (lasso) and bootstrapping-based sparse linear regression methods were suggested in state of the art methods for network inference but they are not effective for a small sample size data and also a true regulator could be missed if the target gene is strongly affected by an indirect regulator with high correlation or another true regulator. We present two novel network inference methods based on the integration of three different criteria, (i) z-score to measure the variation of gene expression from knockout data, (ii) mutual information for the dependency between two genes, and (iii) linear regression-based feature selection. Based on these criterion, we propose a lasso-based random feature selection algorithm (LARF) to achieve better performance overcoming the limitations of bootstrapping as mentioned above. In this work, there are three main contributions. First, our z score-based method to measure gene expression variations from knockout data is more effective than similar criteria of related works. Second, we confirmed that the true regulator selection can be effectively improved by LARF. Lastly, we verified that an integrative approach can clearly outperform a single method when two different methods are effectively jointed. In the experiments, our methods were validated by outperforming the state of the art methods on DREAM challenge data, and then LARF was applied to inferences of gene regulatory network associated with psychiatric disorders.
Reveal, A General Reverse Engineering Algorithm for Inference of Genetic Network Architectures

NASA Technical Reports Server (NTRS)

Liang, Shoudan; Fuhrman, Stefanie; Somogyi, Roland

1998-01-01

Given the immanent gene expression mapping covering whole genomes during development, health and disease, we seek computational methods to maximize functional inference from such large data sets. Is it possible, in principle, to completely infer a complex regulatory network architecture from input/output patterns of its variables? We investigated this possibility using binary models of genetic networks. Trajectories, or state transition tables of Boolean nets, resemble time series of gene expression. By systematically analyzing the mutual information between input states and output states, one is able to infer the sets of input elements controlling each element or gene in the network. This process is unequivocal and exact for complete state transition tables. We implemented this REVerse Engineering ALgorithm (REVEAL) in a C program, and found the problem to be tractable within the conditions tested so far. For n = 50 (elements) and k = 3 (inputs per element), the analysis of incomplete state transition tables (100 state transition pairs out of a possible 10(exp 15)) reliably produced the original rule and wiring sets. While this study is limited to synchronous Boolean networks, the algorithm is generalizable to include multi-state models, essentially allowing direct application to realistic biological data sets. The ability to adequately solve the inverse problem may enable in-depth analysis of complex dynamic systems in biology and other fields.
Probabilistic inference using linear Gaussian importance sampling for hybrid Bayesian networks

NASA Astrophysics Data System (ADS)

Sun, Wei; Chang, K. C.

2005-05-01

Probabilistic inference for Bayesian networks is in general NP-hard using either exact algorithms or approximate methods. However, for very complex networks, only the approximate methods such as stochastic sampling could be used to provide a solution given any time constraint. There are several simulation methods currently available. They include logic sampling (the first proposed stochastic method for Bayesian networks, the likelihood weighting algorithm) the most commonly used simulation method because of its simplicity and efficiency, the Markov blanket scoring method, and the importance sampling algorithm. In this paper, we first briefly review and compare these available simulation methods, then we propose an improved importance sampling algorithm called linear Gaussian importance sampling algorithm for general hybrid model (LGIS). LGIS is aimed for hybrid Bayesian networks consisting of both discrete and continuous random variables with arbitrary distributions. It uses linear function and Gaussian additive noise to approximate the true conditional probability distribution for continuous variable given both its parents and evidence in a Bayesian network. One of the most important features of the newly developed method is that it can adaptively learn the optimal important function from the previous samples. We test the inference performance of LGIS using a 16-node linear Gaussian model and a 6-node general hybrid model. The performance comparison with other well-known methods such as Junction tree (JT) and likelihood weighting (LW) shows that LGIS-GHM is very promising.
Inferring Regulatory Networks from Experimental Morphological Phenotypes: A Computational Method Reverse-Engineers Planarian Regeneration

PubMed Central

Lobo, Daniel; Levin, Michael

2015-01-01

Transformative applications in biomedicine require the discovery of complex regulatory networks that explain the development and regeneration of anatomical structures, and reveal what external signals will trigger desired changes of large-scale pattern. Despite recent advances in bioinformatics, extracting mechanistic pathway models from experimental morphological data is a key open challenge that has resisted automation. The fundamental difficulty of manually predicting emergent behavior of even simple networks has limited the models invented by human scientists to pathway diagrams that show necessary subunit interactions but do not reveal the dynamics that are sufficient for complex, self-regulating pattern to emerge. To finally bridge the gap between high-resolution genetic data and the ability to understand and control patterning, it is critical to develop computational tools to efficiently extract regulatory pathways from the resultant experimental shape phenotypes. For example, planarian regeneration has been studied for over a century, but despite increasing insight into the pathways that control its stem cells, no constructive, mechanistic model has yet been found by human scientists that explains more than one or two key features of its remarkable ability to regenerate its correct anatomical pattern after drastic perturbations. We present a method to infer the molecular products, topology, and spatial and temporal non-linear dynamics of regulatory networks recapitulating in silico the rich dataset of morphological phenotypes resulting from genetic, surgical, and pharmacological experiments. We demonstrated our approach by inferring complete regulatory networks explaining the outcomes of the main functional regeneration experiments in the planarian literature; By analyzing all the datasets together, our system inferred the first systems-biology comprehensive dynamical model explaining patterning in planarian regeneration. This method provides an automated, highly generalizable framework for identifying the underlying control mechanisms responsible for the dynamic regulation of growth and form. PMID:26042810
Boolean network inference from time series data incorporating prior biological knowledge.

PubMed

Haider, Saad; Pal, Ranadip

2012-01-01

Numerous approaches exist for modeling of genetic regulatory networks (GRNs) but the low sampling rates often employed in biological studies prevents the inference of detailed models from experimental data. In this paper, we analyze the issues involved in estimating a model of a GRN from single cell line time series data with limited time points. We present an inference approach for a Boolean Network (BN) model of a GRN from limited transcriptomic or proteomic time series data based on prior biological knowledge of connectivity, constraints on attractor structure and robust design. We applied our inference approach to 6 time point transcriptomic data on Human Mammary Epithelial Cell line (HMEC) after application of Epidermal Growth Factor (EGF) and generated a BN with a plausible biological structure satisfying the data. We further defined and applied a similarity measure to compare synthetic BNs and BNs generated through the proposed approach constructed from transitions of various paths of the synthetic BNs. We have also compared the performance of our algorithm with two existing BN inference algorithms. Through theoretical analysis and simulations, we showed the rarity of arriving at a BN from limited time series data with plausible biological structure using random connectivity and absence of structure in data. The framework when applied to experimental data and data generated from synthetic BNs were able to estimate BNs with high similarity scores. Comparison with existing BN inference algorithms showed the better performance of our proposed algorithm for limited time series data. The proposed framework can also be applied to optimize the connectivity of a GRN from experimental data when the prior biological knowledge on regulators is limited or not unique.
DMirNet: Inferring direct microRNA-mRNA association networks.

PubMed

Lee, Minsu; Lee, HyungJune

2016-12-05

MicroRNAs (miRNAs) play important regulatory roles in the wide range of biological processes by inducing target mRNA degradation or translational repression. Based on the correlation between expression profiles of a miRNA and its target mRNA, various computational methods have previously been proposed to identify miRNA-mRNA association networks by incorporating the matched miRNA and mRNA expression profiles. However, there remain three major issues to be resolved in the conventional computation approaches for inferring miRNA-mRNA association networks from expression profiles. 1) Inferred correlations from the observed expression profiles using conventional correlation-based methods include numerous erroneous links or over-estimated edge weight due to the transitive information flow among direct associations. 2) Due to the high-dimension-low-sample-size problem on the microarray dataset, it is difficult to obtain an accurate and reliable estimate of the empirical correlations between all pairs of expression profiles. 3) Because the previously proposed computational methods usually suffer from varying performance across different datasets, a more reliable model that guarantees optimal or suboptimal performance across different datasets is highly needed. In this paper, we present DMirNet, a new framework for identifying direct miRNA-mRNA association networks. To tackle the aforementioned issues, DMirNet incorporates 1) three direct correlation estimation methods (namely Corpcor, SPACE, Network deconvolution) to infer direct miRNA-mRNA association networks, 2) the bootstrapping method to fully utilize insufficient training expression profiles, and 3) a rank-based Ensemble aggregation to build a reliable and robust model across different datasets. Our empirical experiments on three datasets demonstrate the combinatorial effects of necessary components in DMirNet. Additional performance comparison experiments show that DMirNet outperforms the state-of-the-art Ensemble-based model [1] which has shown the best performance across the same three datasets, with a factor of up to 1.29. Further, we identify 43 putative novel multi-cancer-related miRNA-mRNA association relationships from an inferred Top 1000 direct miRNA-mRNA association network. We believe that DMirNet is a promising method to identify novel direct miRNA-mRNA relations and to elucidate the direct miRNA-mRNA association networks. Since DMirNet infers direct relationships from the observed data, DMirNet can contribute to reconstructing various direct regulatory pathways, including, but not limited to, the direct miRNA-mRNA association networks.
Cross-Dependency Inference in Multi-Layered Networks: A Collaborative Filtering Perspective.

PubMed

Chen, Chen; Tong, Hanghang; Xie, Lei; Ying, Lei; He, Qing

2017-08-01

The increasingly connected world has catalyzed the fusion of networks from different domains, which facilitates the emergence of a new network model-multi-layered networks. Examples of such kind of network systems include critical infrastructure networks, biological systems, organization-level collaborations, cross-platform e-commerce, and so forth. One crucial structure that distances multi-layered network from other network models is its cross-layer dependency, which describes the associations between the nodes from different layers. Needless to say, the cross-layer dependency in the network plays an essential role in many data mining applications like system robustness analysis and complex network control. However, it remains a daunting task to know the exact dependency relationships due to noise, limited accessibility, and so forth. In this article, we tackle the cross-layer dependency inference problem by modeling it as a collective collaborative filtering problem. Based on this idea, we propose an effective algorithm Fascinate that can reveal unobserved dependencies with linear complexity. Moreover, we derive Fascinate-ZERO, an online variant of Fascinate that can respond to a newly added node timely by checking its neighborhood dependencies. We perform extensive evaluations on real datasets to substantiate the superiority of our proposed approaches.
Inverse Ising problem in continuous time: A latent variable approach

NASA Astrophysics Data System (ADS)

Donner, Christian; Opper, Manfred

2017-12-01

We consider the inverse Ising problem: the inference of network couplings from observed spin trajectories for a model with continuous time Glauber dynamics. By introducing two sets of auxiliary latent random variables we render the likelihood into a form which allows for simple iterative inference algorithms with analytical updates. The variables are (1) Poisson variables to linearize an exponential term which is typical for point process likelihoods and (2) Pólya-Gamma variables, which make the likelihood quadratic in the coupling parameters. Using the augmented likelihood, we derive an expectation-maximization (EM) algorithm to obtain the maximum likelihood estimate of network parameters. Using a third set of latent variables we extend the EM algorithm to sparse couplings via L1 regularization. Finally, we develop an efficient approximate Bayesian inference algorithm using a variational approach. We demonstrate the performance of our algorithms on data simulated from an Ising model. For data which are simulated from a more biologically plausible network with spiking neurons, we show that the Ising model captures well the low order statistics of the data and how the Ising couplings are related to the underlying synaptic structure of the simulated network.
Prophetic Granger Causality to infer gene regulatory networks.

PubMed

Carlin, Daniel E; Paull, Evan O; Graim, Kiley; Wong, Christopher K; Bivol, Adrian; Ryabinin, Peter; Ellrott, Kyle; Sokolov, Artem; Stuart, Joshua M

2017-01-01

We introduce a novel method called Prophetic Granger Causality (PGC) for inferring gene regulatory networks (GRNs) from protein-level time series data. The method uses an L1-penalized regression adaptation of Granger Causality to model protein levels as a function of time, stimuli, and other perturbations. When combined with a data-independent network prior, the framework outperformed all other methods submitted to the HPN-DREAM 8 breast cancer network inference challenge. Our investigations reveal that PGC provides complementary information to other approaches, raising the performance of ensemble learners, while on its own achieves moderate performance. Thus, PGC serves as a valuable new tool in the bioinformatics toolkit for analyzing temporal datasets. We investigate the general and cell-specific interactions predicted by our method and find several novel interactions, demonstrating the utility of the approach in charting new tumor wiring.
Prophetic Granger Causality to infer gene regulatory networks

PubMed Central

Carlin, Daniel E.; Paull, Evan O.; Graim, Kiley; Wong, Christopher K.; Bivol, Adrian; Ryabinin, Peter; Ellrott, Kyle; Sokolov, Artem

2017-01-01

We introduce a novel method called Prophetic Granger Causality (PGC) for inferring gene regulatory networks (GRNs) from protein-level time series data. The method uses an L1-penalized regression adaptation of Granger Causality to model protein levels as a function of time, stimuli, and other perturbations. When combined with a data-independent network prior, the framework outperformed all other methods submitted to the HPN-DREAM 8 breast cancer network inference challenge. Our investigations reveal that PGC provides complementary information to other approaches, raising the performance of ensemble learners, while on its own achieves moderate performance. Thus, PGC serves as a valuable new tool in the bioinformatics toolkit for analyzing temporal datasets. We investigate the general and cell-specific interactions predicted by our method and find several novel interactions, demonstrating the utility of the approach in charting new tumor wiring. PMID:29211761
Model based inference from microvascular measurements: Combining experimental measurements and model predictions using a Bayesian probabilistic approach

PubMed Central

Rasmussen, Peter M.; Smith, Amy F.; Sakadžić, Sava; Boas, David A.; Pries, Axel R.; Secomb, Timothy W.; Østergaard, Leif

2017-01-01

Objective In vivo imaging of the microcirculation and network-oriented modeling have emerged as powerful means of studying microvascular function and understanding its physiological significance. Network-oriented modeling may provide the means of summarizing vast amounts of data produced by high-throughput imaging techniques in terms of key, physiological indices. To estimate such indices with sufficient certainty, however, network-oriented analysis must be robust to the inevitable presence of uncertainty due to measurement errors as well as model errors. Methods We propose the Bayesian probabilistic data analysis framework as a means of integrating experimental measurements and network model simulations into a combined and statistically coherent analysis. The framework naturally handles noisy measurements and provides posterior distributions of model parameters as well as physiological indices associated with uncertainty. Results We applied the analysis framework to experimental data from three rat mesentery networks and one mouse brain cortex network. We inferred distributions for more than five hundred unknown pressure and hematocrit boundary conditions. Model predictions were consistent with previous analyses, and remained robust when measurements were omitted from model calibration. Conclusion Our Bayesian probabilistic approach may be suitable for optimizing data acquisition and for analyzing and reporting large datasets acquired as part of microvascular imaging studies. PMID:27987383
Towards Breaking the Histone Code – Bayesian Graphical Models for Histone Modifications

PubMed Central

Mitra, Riten; Müller, Peter; Liang, Shoudan; Xu, Yanxun; Ji, Yuan

2013-01-01

Background Histones are proteins that wrap DNA around in small spherical structures called nucleosomes. Histone modifications (HMs) refer to the post-translational modifications to the histone tails. At a particular genomic locus, each of these HMs can either be present or absent, and the combinatory patterns of the presence or absence of multiple HMs, or the ‘histone codes,’ are believed to co-regulate important biological processes. We aim to use raw data on HM markers at different genomic loci to (1) decode the complex biological network of HMs in a single region and (2) demonstrate how the HM networks differ in different regulatory regions. We suggest that these differences in network attributes form a significant link between histones and genomic functions. Methods and Results We develop a powerful graphical model under Bayesian paradigm. Posterior inference is fully probabilistic, allowing us to compute the probabilities of distinct dependence patterns of the HMs using graphs. Furthermore, our model-based framework allows for easy but important extensions for inference on differential networks under various conditions, such as the different annotations of the genomic locations (e.g., promoters versus insulators). We applied these models to ChIP-Seq data based on CD4+ T lymphocytes. The results confirmed many existing findings and provided a unified tool to generate various promising hypotheses. Differential network analyses revealed new insights on co-regulation of HMs of transcriptional activities in different genomic regions. Conclusions The use of Bayesian graphical models and borrowing strength across different conditions provide high power to infer histone networks and their differences. PMID:23748248
Forecasting of natural gas consumption with neural network and neuro fuzzy system

NASA Astrophysics Data System (ADS)

Kaynar, Oguz; Yilmaz, Isik; Demirkoparan, Ferhan

2010-05-01

The prediction of natural gas consumption is crucial for Turkey which follows foreign-dependent policy in point of providing natural gas and whose stock capacity is only 5% of internal total consumption. Prediction accuracy of demand is one of the elements which has an influence on sectored investments and agreements about obtaining natural gas, so on development of sector. In recent years, new techniques, such as artificial neural networks and fuzzy inference systems, have been widely used in natural gas consumption prediction in addition to classical time series analysis. In this study, weekly natural gas consumption of Turkey has been predicted by means of three different approaches. The first one is Autoregressive Integrated Moving Average (ARIMA), which is classical time series analysis method. The second approach is the Artificial Neural Network. Two different ANN models, which are Multi Layer Perceptron (MLP) and Radial Basis Function Network (RBFN), are employed to predict natural gas consumption. The last is Adaptive Neuro Fuzzy Inference System (ANFIS), which combines ANN and Fuzzy Inference System. Different prediction models have been constructed and one model, which has the best forecasting performance, is determined for each method. Then predictions are made by using these models and results are compared. Keywords: ANN, ANFIS, ARIMA, Natural Gas, Forecasting
Sequential defense against random and intentional attacks in complex networks.

PubMed

Chen, Pin-Yu; Cheng, Shin-Ming

2015-02-01

Network robustness against attacks is one of the most fundamental researches in network science as it is closely associated with the reliability and functionality of various networking paradigms. However, despite the study on intrinsic topological vulnerabilities to node removals, little is known on the network robustness when network defense mechanisms are implemented, especially for networked engineering systems equipped with detection capabilities. In this paper, a sequential defense mechanism is first proposed in complex networks for attack inference and vulnerability assessment, where the data fusion center sequentially infers the presence of an attack based on the binary attack status reported from the nodes in the network. The network robustness is evaluated in terms of the ability to identify the attack prior to network disruption under two major attack schemes, i.e., random and intentional attacks. We provide a parametric plug-in model for performance evaluation on the proposed mechanism and validate its effectiveness and reliability via canonical complex network models and real-world large-scale network topology. The results show that the sequential defense mechanism greatly improves the network robustness and mitigates the possibility of network disruption by acquiring limited attack status information from a small subset of nodes in the network.

Network Inference via the Time-Varying Graphical Lasso

PubMed Central

Hallac, David; Park, Youngsuk; Boyd, Stephen; Leskovec, Jure

2018-01-01

Many important problems can be modeled as a system of interconnected entities, where each entity is recording time-dependent observations or measurements. In order to spot trends, detect anomalies, and interpret the temporal dynamics of such data, it is essential to understand the relationships between the different entities and how these relationships evolve over time. In this paper, we introduce the time-varying graphical lasso (TVGL), a method of inferring time-varying networks from raw time series data. We cast the problem in terms of estimating a sparse time-varying inverse covariance matrix, which reveals a dynamic network of interdependencies between the entities. Since dynamic network inference is a computationally expensive task, we derive a scalable message-passing algorithm based on the Alternating Direction Method of Multipliers (ADMM) to solve this problem in an efficient way. We also discuss several extensions, including a streaming algorithm to update the model and incorporate new observations in real time. Finally, we evaluate our TVGL algorithm on both real and synthetic datasets, obtaining interpretable results and outperforming state-of-the-art baselines in terms of both accuracy and scalability. PMID:29770256
Reconstruction of a Real World Social Network using the Potts Model and Loopy Belief Propagation.

PubMed

Bisconti, Cristian; Corallo, Angelo; Fortunato, Laura; Gentile, Antonio A; Massafra, Andrea; Pellè, Piergiuseppe

2015-01-01

The scope of this paper is to test the adoption of a statistical model derived from Condensed Matter Physics, for the reconstruction of the structure of a social network. The inverse Potts model, traditionally applied to recursive observations of quantum states in an ensemble of particles, is here addressed to observations of the members' states in an organization and their (anti)correlations, thus inferring interactions as links among the members. Adopting proper (Bethe) approximations, such an inverse problem is showed to be tractable. Within an operational framework, this network-reconstruction method is tested for a small real-world social network, the Italian parliament. In this study case, it is easy to track statuses of the parliament members, using (co)sponsorships of law proposals as the initial dataset. In previous studies of similar activity-based networks, the graph structure was inferred directly from activity co-occurrences: here we compare our statistical reconstruction with such standard methods, outlining discrepancies and advantages.
Reconstruction of a Real World Social Network using the Potts Model and Loopy Belief Propagation

PubMed Central

Bisconti, Cristian; Corallo, Angelo; Fortunato, Laura; Gentile, Antonio A.; Massafra, Andrea; Pellè, Piergiuseppe

2015-01-01

The scope of this paper is to test the adoption of a statistical model derived from Condensed Matter Physics, for the reconstruction of the structure of a social network. The inverse Potts model, traditionally applied to recursive observations of quantum states in an ensemble of particles, is here addressed to observations of the members' states in an organization and their (anti)correlations, thus inferring interactions as links among the members. Adopting proper (Bethe) approximations, such an inverse problem is showed to be tractable. Within an operational framework, this network-reconstruction method is tested for a small real-world social network, the Italian parliament. In this study case, it is easy to track statuses of the parliament members, using (co)sponsorships of law proposals as the initial dataset. In previous studies of similar activity-based networks, the graph structure was inferred directly from activity co-occurrences: here we compare our statistical reconstruction with such standard methods, outlining discrepancies and advantages. PMID:26617539
Dynamics on networks: the role of local dynamics and global networks on the emergence of hypersynchronous neural activity.

PubMed

Schmidt, Helmut; Petkov, George; Richardson, Mark P; Terry, John R

2014-11-01

Graph theory has evolved into a useful tool for studying complex brain networks inferred from a variety of measures of neural activity, including fMRI, DTI, MEG and EEG. In the study of neurological disorders, recent work has discovered differences in the structure of graphs inferred from patient and control cohorts. However, most of these studies pursue a purely observational approach; identifying correlations between properties of graphs and the cohort which they describe, without consideration of the underlying mechanisms. To move beyond this necessitates the development of computational modeling approaches to appropriately interpret network interactions and the alterations in brain dynamics they permit, which in the field of complexity sciences is known as dynamics on networks. In this study we describe the development and application of this framework using modular networks of Kuramoto oscillators. We use this framework to understand functional networks inferred from resting state EEG recordings of a cohort of 35 adults with heterogeneous idiopathic generalized epilepsies and 40 healthy adult controls. Taking emergent synchrony across the global network as a proxy for seizures, our study finds that the critical strength of coupling required to synchronize the global network is significantly decreased for the epilepsy cohort for functional networks inferred from both theta (3-6 Hz) and low-alpha (6-9 Hz) bands. We further identify left frontal regions as a potential driver of seizure activity within these networks. We also explore the ability of our method to identify individuals with epilepsy, observing up to 80% predictive power through use of receiver operating characteristic analysis. Collectively these findings demonstrate that a computer model based analysis of routine clinical EEG provides significant additional information beyond standard clinical interpretation, which should ultimately enable a more appropriate mechanistic stratification of people with epilepsy leading to improved diagnostics and therapeutics.
Inferring metabolic networks using the Bayesian adaptive graphical lasso with informative priors.

PubMed

Peterson, Christine; Vannucci, Marina; Karakas, Cemal; Choi, William; Ma, Lihua; Maletić-Savatić, Mirjana

2013-10-01

Metabolic processes are essential for cellular function and survival. We are interested in inferring a metabolic network in activated microglia, a major neuroimmune cell in the brain responsible for the neuroinflammation associated with neurological diseases, based on a set of quantified metabolites. To achieve this, we apply the Bayesian adaptive graphical lasso with informative priors that incorporate known relationships between covariates. To encourage sparsity, the Bayesian graphical lasso places double exponential priors on the off-diagonal entries of the precision matrix. The Bayesian adaptive graphical lasso allows each double exponential prior to have a unique shrinkage parameter. These shrinkage parameters share a common gamma hyperprior. We extend this model to create an informative prior structure by formulating tailored hyperpriors on the shrinkage parameters. By choosing parameter values for each hyperprior that shift probability mass toward zero for nodes that are close together in a reference network, we encourage edges between covariates with known relationships. This approach can improve the reliability of network inference when the sample size is small relative to the number of parameters to be estimated. When applied to the data on activated microglia, the inferred network includes both known relationships and associations of potential interest for further investigation.
Inferring metabolic networks using the Bayesian adaptive graphical lasso with informative priors

PubMed Central

PETERSON, CHRISTINE; VANNUCCI, MARINA; KARAKAS, CEMAL; CHOI, WILLIAM; MA, LIHUA; MALETIĆ-SAVATIĆ, MIRJANA

2014-01-01

Metabolic processes are essential for cellular function and survival. We are interested in inferring a metabolic network in activated microglia, a major neuroimmune cell in the brain responsible for the neuroinflammation associated with neurological diseases, based on a set of quantified metabolites. To achieve this, we apply the Bayesian adaptive graphical lasso with informative priors that incorporate known relationships between covariates. To encourage sparsity, the Bayesian graphical lasso places double exponential priors on the off-diagonal entries of the precision matrix. The Bayesian adaptive graphical lasso allows each double exponential prior to have a unique shrinkage parameter. These shrinkage parameters share a common gamma hyperprior. We extend this model to create an informative prior structure by formulating tailored hyperpriors on the shrinkage parameters. By choosing parameter values for each hyperprior that shift probability mass toward zero for nodes that are close together in a reference network, we encourage edges between covariates with known relationships. This approach can improve the reliability of network inference when the sample size is small relative to the number of parameters to be estimated. When applied to the data on activated microglia, the inferred network includes both known relationships and associations of potential interest for further investigation. PMID:24533172
Inference of Transmission Network Structure from HIV Phylogenetic Trees

DOE PAGES

Giardina, Federica; Romero-Severson, Ethan Obie; Albert, Jan; ...

2017-01-13

Phylogenetic inference is an attractive means to reconstruct transmission histories and epidemics. However, there is not a perfect correspondence between transmission history and virus phylogeny. Both node height and topological differences may occur, depending on the interaction between within-host evolutionary dynamics and between-host transmission patterns. To investigate these interactions, we added a within-host evolutionary model in epidemiological simulations and examined if the resulting phylogeny could recover different types of contact networks. To further improve realism, we also introduced patient-specific differences in infectivity across disease stages, and on the epidemic level we considered incomplete sampling and the age of the epidemic.more » Second, we implemented an inference method based on approximate Bayesian computation (ABC) to discriminate among three well-studied network models and jointly estimate both network parameters and key epidemiological quantities such as the infection rate. Our ABC framework used both topological and distance-based tree statistics for comparison between simulated and observed trees. Overall, our simulations showed that a virus time-scaled phylogeny (genealogy) may be substantially different from the between-host transmission tree. This has important implications for the interpretation of what a phylogeny reveals about the underlying epidemic contact network. In particular, we found that while the within-host evolutionary process obscures the transmission tree, the diversification process and infectivity dynamics also add discriminatory power to differentiate between different types of contact networks. We also found that the possibility to differentiate contact networks depends on how far an epidemic has progressed, where distance-based tree statistics have more power early in an epidemic. Finally, we applied our ABC inference on two different outbreaks from the Swedish HIV-1 epidemic.« less
Inference of Transmission Network Structure from HIV Phylogenetic Trees

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giardina, Federica; Romero-Severson, Ethan Obie; Albert, Jan

Phylogenetic inference is an attractive means to reconstruct transmission histories and epidemics. However, there is not a perfect correspondence between transmission history and virus phylogeny. Both node height and topological differences may occur, depending on the interaction between within-host evolutionary dynamics and between-host transmission patterns. To investigate these interactions, we added a within-host evolutionary model in epidemiological simulations and examined if the resulting phylogeny could recover different types of contact networks. To further improve realism, we also introduced patient-specific differences in infectivity across disease stages, and on the epidemic level we considered incomplete sampling and the age of the epidemic.more » Second, we implemented an inference method based on approximate Bayesian computation (ABC) to discriminate among three well-studied network models and jointly estimate both network parameters and key epidemiological quantities such as the infection rate. Our ABC framework used both topological and distance-based tree statistics for comparison between simulated and observed trees. Overall, our simulations showed that a virus time-scaled phylogeny (genealogy) may be substantially different from the between-host transmission tree. This has important implications for the interpretation of what a phylogeny reveals about the underlying epidemic contact network. In particular, we found that while the within-host evolutionary process obscures the transmission tree, the diversification process and infectivity dynamics also add discriminatory power to differentiate between different types of contact networks. We also found that the possibility to differentiate contact networks depends on how far an epidemic has progressed, where distance-based tree statistics have more power early in an epidemic. Finally, we applied our ABC inference on two different outbreaks from the Swedish HIV-1 epidemic.« less
CGBayesNets: Conditional Gaussian Bayesian Network Learning and Inference with Mixed Discrete and Continuous Data

PubMed Central

Weiss, Scott T.

2014-01-01

Bayesian Networks (BN) have been a popular predictive modeling formalism in bioinformatics, but their application in modern genomics has been slowed by an inability to cleanly handle domains with mixed discrete and continuous variables. Existing free BN software packages either discretize continuous variables, which can lead to information loss, or do not include inference routines, which makes prediction with the BN impossible. We present CGBayesNets, a BN package focused around prediction of a clinical phenotype from mixed discrete and continuous variables, which fills these gaps. CGBayesNets implements Bayesian likelihood and inference algorithms for the conditional Gaussian Bayesian network (CGBNs) formalism, one appropriate for predicting an outcome of interest from, e.g., multimodal genomic data. We provide four different network learning algorithms, each making a different tradeoff between computational cost and network likelihood. CGBayesNets provides a full suite of functions for model exploration and verification, including cross validation, bootstrapping, and AUC manipulation. We highlight several results obtained previously with CGBayesNets, including predictive models of wood properties from tree genomics, leukemia subtype classification from mixed genomic data, and robust prediction of intensive care unit mortality outcomes from metabolomic profiles. We also provide detailed example analysis on public metabolomic and gene expression datasets. CGBayesNets is implemented in MATLAB and available as MATLAB source code, under an Open Source license and anonymous download at http://www.cgbayesnets.com. PMID:24922310
CGBayesNets: conditional Gaussian Bayesian network learning and inference with mixed discrete and continuous data.

PubMed

McGeachie, Michael J; Chang, Hsun-Hsien; Weiss, Scott T

2014-06-01

Bayesian Networks (BN) have been a popular predictive modeling formalism in bioinformatics, but their application in modern genomics has been slowed by an inability to cleanly handle domains with mixed discrete and continuous variables. Existing free BN software packages either discretize continuous variables, which can lead to information loss, or do not include inference routines, which makes prediction with the BN impossible. We present CGBayesNets, a BN package focused around prediction of a clinical phenotype from mixed discrete and continuous variables, which fills these gaps. CGBayesNets implements Bayesian likelihood and inference algorithms for the conditional Gaussian Bayesian network (CGBNs) formalism, one appropriate for predicting an outcome of interest from, e.g., multimodal genomic data. We provide four different network learning algorithms, each making a different tradeoff between computational cost and network likelihood. CGBayesNets provides a full suite of functions for model exploration and verification, including cross validation, bootstrapping, and AUC manipulation. We highlight several results obtained previously with CGBayesNets, including predictive models of wood properties from tree genomics, leukemia subtype classification from mixed genomic data, and robust prediction of intensive care unit mortality outcomes from metabolomic profiles. We also provide detailed example analysis on public metabolomic and gene expression datasets. CGBayesNets is implemented in MATLAB and available as MATLAB source code, under an Open Source license and anonymous download at http://www.cgbayesnets.com.
Gene network inference and visualization tools for biologists: application to new human transcriptome datasets

PubMed Central

Hurley, Daniel; Araki, Hiromitsu; Tamada, Yoshinori; Dunmore, Ben; Sanders, Deborah; Humphreys, Sally; Affara, Muna; Imoto, Seiya; Yasuda, Kaori; Tomiyasu, Yuki; Tashiro, Kosuke; Savoie, Christopher; Cho, Vicky; Smith, Stephen; Kuhara, Satoru; Miyano, Satoru; Charnock-Jones, D. Stephen; Crampin, Edmund J.; Print, Cristin G.

2012-01-01

Gene regulatory networks inferred from RNA abundance data have generated significant interest, but despite this, gene network approaches are used infrequently and often require input from bioinformaticians. We have assembled a suite of tools for analysing regulatory networks, and we illustrate their use with microarray datasets generated in human endothelial cells. We infer a range of regulatory networks, and based on this analysis discuss the strengths and limitations of network inference from RNA abundance data. We welcome contact from researchers interested in using our inference and visualization tools to answer biological questions. PMID:22121215
TRACING CO-REGULATORY NETWORK DYNAMICS IN NOISY, SINGLE-CELL TRANSCRIPTOME TRAJECTORIES.

PubMed

Cordero, Pablo; Stuart, Joshua M

2017-01-01

The availability of gene expression data at the single cell level makes it possible to probe the molecular underpinnings of complex biological processes such as differentiation and oncogenesis. Promising new methods have emerged for reconstructing a progression 'trajectory' from static single-cell transcriptome measurements. However, it remains unclear how to adequately model the appreciable level of noise in these data to elucidate gene regulatory network rewiring. Here, we present a framework called Single Cell Inference of MorphIng Trajectories and their Associated Regulation (SCIMITAR) that infers progressions from static single-cell transcriptomes by employing a continuous parametrization of Gaussian mixtures in high-dimensional curves. SCIMITAR yields rich models from the data that highlight genes with expression and co-expression patterns that are associated with the inferred progression. Further, SCIMITAR extracts regulatory states from the implicated trajectory-evolvingco-expression networks. We benchmark the method on simulated data to show that it yields accurate cell ordering and gene network inferences. Applied to the interpretation of a single-cell human fetal neuron dataset, SCIMITAR finds progression-associated genes in cornerstone neural differentiation pathways missed by standard differential expression tests. Finally, by leveraging the rewiring of gene-gene co-expression relations across the progression, the method reveals the rise and fall of co-regulatory states and trajectory-dependent gene modules. These analyses implicate new transcription factors in neural differentiation including putative co-factors for the multi-functional NFAT pathway.
Active learning of cortical connectivity from two-photon imaging data.

PubMed

Bertrán, Martín A; Martínez, Natalia L; Wang, Ye; Dunson, David; Sapiro, Guillermo; Ringach, Dario

2018-01-01

Understanding how groups of neurons interact within a network is a fundamental question in system neuroscience. Instead of passively observing the ongoing activity of a network, we can typically perturb its activity, either by external sensory stimulation or directly via techniques such as two-photon optogenetics. A natural question is how to use such perturbations to identify the connectivity of the network efficiently. Here we introduce a method to infer sparse connectivity graphs from in-vivo, two-photon imaging of population activity in response to external stimuli. A novel aspect of the work is the introduction of a recommended distribution, incrementally learned from the data, to optimally refine the inferred network. Unlike existing system identification techniques, this "active learning" method automatically focuses its attention on key undiscovered areas of the network, instead of targeting global uncertainty indicators like parameter variance. We show how active learning leads to faster inference while, at the same time, provides confidence intervals for the network parameters. We present simulations on artificial small-world networks to validate the methods and apply the method to real data. Analysis of frequency of motifs recovered show that cortical networks are consistent with a small-world topology model.
Active learning of cortical connectivity from two-photon imaging data

PubMed Central

Wang, Ye; Dunson, David; Sapiro, Guillermo; Ringach, Dario

2018-01-01

Understanding how groups of neurons interact within a network is a fundamental question in system neuroscience. Instead of passively observing the ongoing activity of a network, we can typically perturb its activity, either by external sensory stimulation or directly via techniques such as two-photon optogenetics. A natural question is how to use such perturbations to identify the connectivity of the network efficiently. Here we introduce a method to infer sparse connectivity graphs from in-vivo, two-photon imaging of population activity in response to external stimuli. A novel aspect of the work is the introduction of a recommended distribution, incrementally learned from the data, to optimally refine the inferred network. Unlike existing system identification techniques, this “active learning” method automatically focuses its attention on key undiscovered areas of the network, instead of targeting global uncertainty indicators like parameter variance. We show how active learning leads to faster inference while, at the same time, provides confidence intervals for the network parameters. We present simulations on artificial small-world networks to validate the methods and apply the method to real data. Analysis of frequency of motifs recovered show that cortical networks are consistent with a small-world topology model. PMID:29718955
In silico model-based inference: a contemporary approach for hypothesis testing in network biology

PubMed Central

Klinke, David J.

2014-01-01

Inductive inference plays a central role in the study of biological systems where one aims to increase their understanding of the system by reasoning backwards from uncertain observations to identify causal relationships among components of the system. These causal relationships are postulated from prior knowledge as a hypothesis or simply a model. Experiments are designed to test the model. Inferential statistics are used to establish a level of confidence in how well our postulated model explains the acquired data. This iterative process, commonly referred to as the scientific method, either improves our confidence in a model or suggests that we revisit our prior knowledge to develop a new model. Advances in technology impact how we use prior knowledge and data to formulate models of biological networks and how we observe cellular behavior. However, the approach for model-based inference has remained largely unchanged since Fisher, Neyman and Pearson developed the ideas in the early 1900’s that gave rise to what is now known as classical statistical hypothesis (model) testing. Here, I will summarize conventional methods for model-based inference and suggest a contemporary approach to aid in our quest to discover how cells dynamically interpret and transmit information for therapeutic aims that integrates ideas drawn from high performance computing, Bayesian statistics, and chemical kinetics. PMID:25139179
In silico model-based inference: a contemporary approach for hypothesis testing in network biology.

PubMed

Klinke, David J

2014-01-01

Inductive inference plays a central role in the study of biological systems where one aims to increase their understanding of the system by reasoning backwards from uncertain observations to identify causal relationships among components of the system. These causal relationships are postulated from prior knowledge as a hypothesis or simply a model. Experiments are designed to test the model. Inferential statistics are used to establish a level of confidence in how well our postulated model explains the acquired data. This iterative process, commonly referred to as the scientific method, either improves our confidence in a model or suggests that we revisit our prior knowledge to develop a new model. Advances in technology impact how we use prior knowledge and data to formulate models of biological networks and how we observe cellular behavior. However, the approach for model-based inference has remained largely unchanged since Fisher, Neyman and Pearson developed the ideas in the early 1900s that gave rise to what is now known as classical statistical hypothesis (model) testing. Here, I will summarize conventional methods for model-based inference and suggest a contemporary approach to aid in our quest to discover how cells dynamically interpret and transmit information for therapeutic aims that integrates ideas drawn from high performance computing, Bayesian statistics, and chemical kinetics. © 2014 American Institute of Chemical Engineers.
Data identification for improving gene network inference using computational algebra.

PubMed

Dimitrova, Elena; Stigler, Brandilyn

2014-11-01

Identification of models of gene regulatory networks is sensitive to the amount of data used as input. Considering the substantial costs in conducting experiments, it is of value to have an estimate of the amount of data required to infer the network structure. To minimize wasted resources, it is also beneficial to know which data are necessary to identify the network. Knowledge of the data and knowledge of the terms in polynomial models are often required a priori in model identification. In applications, it is unlikely that the structure of a polynomial model will be known, which may force data sets to be unnecessarily large in order to identify a model. Furthermore, none of the known results provides any strategy for constructing data sets to uniquely identify a model. We provide a specialization of an existing criterion for deciding when a set of data points identifies a minimal polynomial model when its monomial terms have been specified. Then, we relax the requirement of the knowledge of the monomials and present results for model identification given only the data. Finally, we present a method for constructing data sets that identify minimal polynomial models.
A decision network account of reasoning about other people's choices

PubMed Central

Jern, Alan; Kemp, Charles

2015-01-01

The ability to predict and reason about other people's choices is fundamental to social interaction. We propose that people reason about other people's choices using mental models that are similar to decision networks. Decision networks are extensions of Bayesian networks that incorporate the idea that choices are made in order to achieve goals. In our first experiment, we explore how people predict the choices of others. Our remaining three experiments explore how people infer the goals and knowledge of others by observing the choices that they make. We show that decision networks account for our data better than alternative computational accounts that do not incorporate the notion of goal-directed choice or that do not rely on probabilistic inference. PMID:26010559
Mental Models of Invisible Logical Networks

NASA Technical Reports Server (NTRS)

Sanderson, P.

1984-01-01

Subjects were required to discover the structure of a logical network whose links were invisible. Network structure had to be inferred from the behavior of the components after a failure. It was hypothesized that since such failure diagnosis tasks often draw on spatial processes, a good deal of spatial complexity in the network should affect network discovery. Results show that the ability to discover the linkages in the network is directly related to the spatial complexity of the pathway described by the linkages. This effect was generally independent of the amount of evidence available to subjects about the existence of the link. These results raise the question of whether inferences about spatially complex pathways were simply not made, or whether they were made but not retained because of a high load on memory resources.
Experiments on neural network architectures for fuzzy logic

NASA Technical Reports Server (NTRS)

Keller, James M.

1991-01-01

The use of fuzzy logic to model and manage uncertainty in a rule-based system places high computational demands on an inference engine. In an earlier paper, the authors introduced a trainable neural network structure for fuzzy logic. These networks can learn and extrapolate complex relationships between possibility distributions for the antecedents and consequents in the rules. Here, the power of these networks is further explored. The insensitivity of the output to noisy input distributions (which are likely if the clauses are generated from real data) is demonstrated as well as the ability of the networks to internalize multiple conjunctive clause and disjunctive clause rules. Since different rules with the same variables can be encoded in a single network, this approach to fuzzy logic inference provides a natural mechanism for rule conflict resolution.

A linear programming computational framework integrates phosphor-proteomics and prior knowledge to predict drug efficacy.

PubMed

Ji, Zhiwei; Wang, Bing; Yan, Ke; Dong, Ligang; Meng, Guanmin; Shi, Lei

2017-12-21

In recent years, the integration of 'omics' technologies, high performance computation, and mathematical modeling of biological processes marks that the systems biology has started to fundamentally impact the way of approaching drug discovery. The LINCS public data warehouse provides detailed information about cell responses with various genetic and environmental stressors. It can be greatly helpful in developing new drugs and therapeutics, as well as improving the situations of lacking effective drugs, drug resistance and relapse in cancer therapies, etc. In this study, we developed a Ternary status based Integer Linear Programming (TILP) method to infer cell-specific signaling pathway network and predict compounds' treatment efficacy. The novelty of our study is that phosphor-proteomic data and prior knowledge are combined for modeling and optimizing the signaling network. To test the power of our approach, a generic pathway network was constructed for a human breast cancer cell line MCF7; and the TILP model was used to infer MCF7-specific pathways with a set of phosphor-proteomic data collected from ten representative small molecule chemical compounds (most of them were studied in breast cancer treatment). Cross-validation indicated that the MCF7-specific pathway network inferred by TILP were reliable predicting a compound's efficacy. Finally, we applied TILP to re-optimize the inferred cell-specific pathways and predict the outcomes of five small compounds (carmustine, doxorubicin, GW-8510, daunorubicin, and verapamil), which were rarely used in clinic for breast cancer. In the simulation, the proposed approach facilitates us to identify a compound's treatment efficacy qualitatively and quantitatively, and the cross validation analysis indicated good accuracy in predicting effects of five compounds. In summary, the TILP model is useful for discovering new drugs for clinic use, and also elucidating the potential mechanisms of a compound to targets.
BiomeNet: A Bayesian Model for Inference of Metabolic Divergence among Microbial Communities

PubMed Central

Chipman, Hugh; Gu, Hong; Bielawski, Joseph P.

2014-01-01

Metagenomics yields enormous numbers of microbial sequences that can be assigned a metabolic function. Using such data to infer community-level metabolic divergence is hindered by the lack of a suitable statistical framework. Here, we describe a novel hierarchical Bayesian model, called BiomeNet (Bayesian inference of metabolic networks), for inferring differential prevalence of metabolic subnetworks among microbial communities. To infer the structure of community-level metabolic interactions, BiomeNet applies a mixed-membership modelling framework to enzyme abundance information. The basic idea is that the mixture components of the model (metabolic reactions, subnetworks, and networks) are shared across all groups (microbiome samples), but the mixture proportions vary from group to group. Through this framework, the model can capture nested structures within the data. BiomeNet is unique in modeling each metagenome sample as a mixture of complex metabolic systems (metabosystems). The metabosystems are composed of mixtures of tightly connected metabolic subnetworks. BiomeNet differs from other unsupervised methods by allowing researchers to discriminate groups of samples through the metabolic patterns it discovers in the data, and by providing a framework for interpreting them. We describe a collapsed Gibbs sampler for inference of the mixture weights under BiomeNet, and we use simulation to validate the inference algorithm. Application of BiomeNet to human gut metagenomes revealed a metabosystem with greater prevalence among inflammatory bowel disease (IBD) patients. Based on the discriminatory subnetworks for this metabosystem, we inferred that the community is likely to be closely associated with the human gut epithelium, resistant to dietary interventions, and interfere with human uptake of an antioxidant connected to IBD. Because this metabosystem has a greater capacity to exploit host-associated glycans, we speculate that IBD-associated communities might arise from opportunist growth of bacteria that can circumvent the host's nutrient-based mechanism for bacterial partner selection. PMID:25412107
On the inherent competition between valid and spurious inductive inferences in Boolean data

NASA Astrophysics Data System (ADS)

Andrecut, M.

Inductive inference is the process of extracting general rules from specific observations. This problem also arises in the analysis of biological networks, such as genetic regulatory networks, where the interactions are complex and the observations are incomplete. A typical task in these problems is to extract general interaction rules as combinations of Boolean covariates, that explain a measured response variable. The inductive inference process can be considered as an incompletely specified Boolean function synthesis problem. This incompleteness of the problem will also generate spurious inferences, which are a serious threat to valid inductive inference rules. Using random Boolean data as a null model, here we attempt to measure the competition between valid and spurious inductive inference rules from a given data set. We formulate two greedy search algorithms, which synthesize a given Boolean response variable in a sparse disjunct normal form, and respectively a sparse generalized algebraic normal form of the variables from the observation data, and we evaluate numerically their performance.
Inferring anatomical therapeutic chemical (ATC) class of drugs using shortest path and random walk with restart algorithms.

PubMed

Chen, Lei; Liu, Tao; Zhao, Xian

2018-06-01

The anatomical therapeutic chemical (ATC) classification system is a widely accepted drug classification scheme. This system comprises five levels and includes several classes in each level. Drugs are classified into classes according to their therapeutic effects and characteristics. The first level includes 14 main classes. In this study, we proposed two network-based models to infer novel potential chemicals deemed to belong in the first level of ATC classification. To build these models, two large chemical networks were constructed using the chemical-chemical interaction information retrieved from the Search Tool for Interactions of Chemicals (STITCH). Two classic network algorithms, shortest path (SP) and random walk with restart (RWR) algorithms, were executed on the corresponding network to mine novel chemicals for each ATC class using the validated drugs in a class as seed nodes. Then, the obtained chemicals yielded by these two algorithms were further evaluated by a permutation test and an association test. The former can exclude chemicals produced by the structure of the network, i.e., false positive discoveries. By contrast, the latter identifies the most important chemicals that have strong associations with the ATC class. Comparisons indicated that the two models can provide quite dissimilar results, suggesting that the results yielded by one model can be essential supplements for those obtained by the other model. In addition, several representative inferred chemicals were analyzed to confirm the reliability of the results generated by the two models. This article is part of a Special Issue entitled: Accelerating Precision Medicine through Genetic and Genomic Big Data Analysis edited by Yudong Cai & Tao Huang. Copyright © 2017 Elsevier B.V. All rights reserved.
Impact of environmental inputs on reverse-engineering approach to network structures.

PubMed

Wu, Jianhua; Sinfield, James L; Buchanan-Wollaston, Vicky; Feng, Jianfeng

2009-12-04

Uncovering complex network structures from a biological system is one of the main topic in system biology. The network structures can be inferred by the dynamical Bayesian network or Granger causality, but neither techniques have seriously taken into account the impact of environmental inputs. With considerations of natural rhythmic dynamics of biological data, we propose a system biology approach to reveal the impact of environmental inputs on network structures. We first represent the environmental inputs by a harmonic oscillator and combine them with Granger causality to identify environmental inputs and then uncover the causal network structures. We also generalize it to multiple harmonic oscillators to represent various exogenous influences. This system approach is extensively tested with toy models and successfully applied to a real biological network of microarray data of the flowering genes of the model plant Arabidopsis Thaliana. The aim is to identify those genes that are directly affected by the presence of the sunlight and uncover the interactive network structures associating with flowering metabolism. We demonstrate that environmental inputs are crucial for correctly inferring network structures. Harmonic causal method is proved to be a powerful technique to detect environment inputs and uncover network structures, especially when the biological data exhibit periodic oscillations.
Inference and Analysis of Population Structure Using Genetic Data and Network Theory

PubMed Central

Greenbaum, Gili; Templeton, Alan R.; Bar-David, Shirli

2016-01-01

Clustering individuals to subpopulations based on genetic data has become commonplace in many genetic studies. Inference about population structure is most often done by applying model-based approaches, aided by visualization using distance-based approaches such as multidimensional scaling. While existing distance-based approaches suffer from a lack of statistical rigor, model-based approaches entail assumptions of prior conditions such as that the subpopulations are at Hardy-Weinberg equilibria. Here we present a distance-based approach for inference about population structure using genetic data by defining population structure using network theory terminology and methods. A network is constructed from a pairwise genetic-similarity matrix of all sampled individuals. The community partition, a partition of a network to dense subgraphs, is equated with population structure, a partition of the population to genetically related groups. Community-detection algorithms are used to partition the network into communities, interpreted as a partition of the population to subpopulations. The statistical significance of the structure can be estimated by using permutation tests to evaluate the significance of the partition’s modularity, a network theory measure indicating the quality of community partitions. To further characterize population structure, a new measure of the strength of association (SA) for an individual to its assigned community is presented. The strength of association distribution (SAD) of the communities is analyzed to provide additional population structure characteristics, such as the relative amount of gene flow experienced by the different subpopulations and identification of hybrid individuals. Human genetic data and simulations are used to demonstrate the applicability of the analyses. The approach presented here provides a novel, computationally efficient model-free method for inference about population structure that does not entail assumption of prior conditions. The method is implemented in the software NetStruct (available at https://giligreenbaum.wordpress.com/software/). PMID:26888080
Inference and Analysis of Population Structure Using Genetic Data and Network Theory.

PubMed

Greenbaum, Gili; Templeton, Alan R; Bar-David, Shirli

2016-04-01

Clustering individuals to subpopulations based on genetic data has become commonplace in many genetic studies. Inference about population structure is most often done by applying model-based approaches, aided by visualization using distance-based approaches such as multidimensional scaling. While existing distance-based approaches suffer from a lack of statistical rigor, model-based approaches entail assumptions of prior conditions such as that the subpopulations are at Hardy-Weinberg equilibria. Here we present a distance-based approach for inference about population structure using genetic data by defining population structure using network theory terminology and methods. A network is constructed from a pairwise genetic-similarity matrix of all sampled individuals. The community partition, a partition of a network to dense subgraphs, is equated with population structure, a partition of the population to genetically related groups. Community-detection algorithms are used to partition the network into communities, interpreted as a partition of the population to subpopulations. The statistical significance of the structure can be estimated by using permutation tests to evaluate the significance of the partition's modularity, a network theory measure indicating the quality of community partitions. To further characterize population structure, a new measure of the strength of association (SA) for an individual to its assigned community is presented. The strength of association distribution (SAD) of the communities is analyzed to provide additional population structure characteristics, such as the relative amount of gene flow experienced by the different subpopulations and identification of hybrid individuals. Human genetic data and simulations are used to demonstrate the applicability of the analyses. The approach presented here provides a novel, computationally efficient model-free method for inference about population structure that does not entail assumption of prior conditions. The method is implemented in the software NetStruct (available at https://giligreenbaum.wordpress.com/software/). Copyright © 2016 by the Genetics Society of America.
Identification of Boolean Network Models From Time Series Data Incorporating Prior Knowledge.

PubMed

Leifeld, Thomas; Zhang, Zhihua; Zhang, Ping

2018-01-01

Motivation: Mathematical models take an important place in science and engineering. A model can help scientists to explain dynamic behavior of a system and to understand the functionality of system components. Since length of a time series and number of replicates is limited by the cost of experiments, Boolean networks as a structurally simple and parameter-free logical model for gene regulatory networks have attracted interests of many scientists. In order to fit into the biological contexts and to lower the data requirements, biological prior knowledge is taken into consideration during the inference procedure. In the literature, the existing identification approaches can only deal with a subset of possible types of prior knowledge. Results: We propose a new approach to identify Boolean networks from time series data incorporating prior knowledge, such as partial network structure, canalizing property, positive and negative unateness. Using vector form of Boolean variables and applying a generalized matrix multiplication called the semi-tensor product (STP), each Boolean function can be equivalently converted into a matrix expression. Based on this, the identification problem is reformulated as an integer linear programming problem to reveal the system matrix of Boolean model in a computationally efficient way, whose dynamics are consistent with the important dynamics captured in the data. By using prior knowledge the number of candidate functions can be reduced during the inference. Hence, identification incorporating prior knowledge is especially suitable for the case of small size time series data and data without sufficient stimuli. The proposed approach is illustrated with the help of a biological model of the network of oxidative stress response. Conclusions: The combination of efficient reformulation of the identification problem with the possibility to incorporate various types of prior knowledge enables the application of computational model inference to systems with limited amount of time series data. The general applicability of this methodological approach makes it suitable for a variety of biological systems and of general interest for biological and medical research.
Spectral Entropies as Information-Theoretic Tools for Complex Network Comparison

NASA Astrophysics Data System (ADS)

De Domenico, Manlio; Biamonte, Jacob

2016-10-01

Any physical system can be viewed from the perspective that information is implicitly represented in its state. However, the quantification of this information when it comes to complex networks has remained largely elusive. In this work, we use techniques inspired by quantum statistical mechanics to define an entropy measure for complex networks and to develop a set of information-theoretic tools, based on network spectral properties, such as Rényi q entropy, generalized Kullback-Leibler and Jensen-Shannon divergences, the latter allowing us to define a natural distance measure between complex networks. First, we show that by minimizing the Kullback-Leibler divergence between an observed network and a parametric network model, inference of model parameter(s) by means of maximum-likelihood estimation can be achieved and model selection can be performed with appropriate information criteria. Second, we show that the information-theoretic metric quantifies the distance between pairs of networks and we can use it, for instance, to cluster the layers of a multilayer system. By applying this framework to networks corresponding to sites of the human microbiome, we perform hierarchical cluster analysis and recover with high accuracy existing community-based associations. Our results imply that spectral-based statistical inference in complex networks results in demonstrably superior performance as well as a conceptual backbone, filling a gap towards a network information theory.
Reverse engineering biological networks :applications in immune responses to bio-toxins.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martino, Anthony A.; Sinclair, Michael B.; Davidson, George S.

Our aim is to determine the network of events, or the regulatory network, that defines an immune response to a bio-toxin. As a model system, we are studying T cell regulatory network triggered through tyrosine kinase receptor activation using a combination of pathway stimulation and time-series microarray experiments. Our approach is composed of five steps (1) microarray experiments and data error analysis, (2) data clustering, (3) data smoothing and discretization, (4) network reverse engineering, and (5) network dynamics analysis and fingerprint identification. The technological outcome of this study is a suite of experimental protocols and computational tools that reverse engineermore » regulatory networks provided gene expression data. The practical biological outcome of this work is an immune response fingerprint in terms of gene expression levels. Inferring regulatory networks from microarray data is a new field of investigation that is no more than five years old. To the best of our knowledge, this work is the first attempt that integrates experiments, error analyses, data clustering, inference, and network analysis to solve a practical problem. Our systematic approach of counting, enumeration, and sampling networks matching experimental data is new to the field of network reverse engineering. The resulting mathematical analyses and computational tools lead to new results on their own and should be useful to others who analyze and infer networks.« less
MapReduce Algorithms for Inferring Gene Regulatory Networks from Time-Series Microarray Data Using an Information-Theoretic Approach.

PubMed

Abduallah, Yasser; Turki, Turki; Byron, Kevin; Du, Zongxuan; Cervantes-Cervantes, Miguel; Wang, Jason T L

2017-01-01

Gene regulation is a series of processes that control gene expression and its extent. The connections among genes and their regulatory molecules, usually transcription factors, and a descriptive model of such connections are known as gene regulatory networks (GRNs). Elucidating GRNs is crucial to understand the inner workings of the cell and the complexity of gene interactions. To date, numerous algorithms have been developed to infer gene regulatory networks. However, as the number of identified genes increases and the complexity of their interactions is uncovered, networks and their regulatory mechanisms become cumbersome to test. Furthermore, prodding through experimental results requires an enormous amount of computation, resulting in slow data processing. Therefore, new approaches are needed to expeditiously analyze copious amounts of experimental data resulting from cellular GRNs. To meet this need, cloud computing is promising as reported in the literature. Here, we propose new MapReduce algorithms for inferring gene regulatory networks on a Hadoop cluster in a cloud environment. These algorithms employ an information-theoretic approach to infer GRNs using time-series microarray data. Experimental results show that our MapReduce program is much faster than an existing tool while achieving slightly better prediction accuracy than the existing tool.
Novel application of multi-stimuli network inference to synovial fibroblasts of rheumatoid arthritis patients

PubMed Central

2014-01-01

Background Network inference of gene expression data is an important challenge in systems biology. Novel algorithms may provide more detailed gene regulatory networks (GRN) for complex, chronic inflammatory diseases such as rheumatoid arthritis (RA), in which activated synovial fibroblasts (SFBs) play a major role. Since the detailed mechanisms underlying this activation are still unclear, simultaneous investigation of multi-stimuli activation of SFBs offers the possibility to elucidate the regulatory effects of multiple mediators and to gain new insights into disease pathogenesis. Methods A GRN was therefore inferred from RA-SFBs treated with 4 different stimuli (IL-1 β, TNF- α, TGF- β, and PDGF-D). Data from time series microarray experiments (0, 1, 2, 4, 12 h; Affymetrix HG-U133 Plus 2.0) were batch-corrected applying ‘ComBat’, analyzed for differentially expressed genes over time with ‘Limma’, and used for the inference of a robust GRN with NetGenerator V2.0, a heuristic ordinary differential equation-based method with soft integration of prior knowledge. Results Using all genes differentially expressed over time in RA-SFBs for any stimulus, and selecting the genes belonging to the most significant gene ontology (GO) term, i.e., ‘cartilage development’, a dynamic, robust, moderately complex multi-stimuli GRN was generated with 24 genes and 57 edges in total, 31 of which were gene-to-gene edges. Prior literature-based knowledge derived from Pathway Studio or manual searches was reflected in the final network by 25/57 confirmed edges (44%). The model contained known network motifs crucial for dynamic cellular behavior, e.g., cross-talk among pathways, positive feed-back loops, and positive feed-forward motifs (including suppression of the transcriptional repressor OSR2 by all 4 stimuli. Conclusion A multi-stimuli GRN highly concordant with literature data was successfully generated by network inference from the gene expression of stimulated RA-SFBs. The GRN showed high reliability, since 10 predicted edges were independently validated by literature findings post network inference. The selected GO term ‘cartilage development’ contained a number of differentiation markers, growth factors, and transcription factors with potential relevance for RA. Finally, the model provided new insight into the response of RA-SFBs to multiple stimuli implicated in the pathogenesis of RA, in particular to the ‘novel’ potent growth factor PDGF-D. PMID:24989895
Inferring Weighted Directed Association Network from Multivariate Time Series with a Synthetic Method of Partial Symbolic Transfer Entropy Spectrum and Granger Causality

PubMed Central

Hu, Yanzhu; Ai, Xinbo

2016-01-01

Complex network methodology is very useful for complex system explorer. However, the relationships among variables in complex system are usually not clear. Therefore, inferring association networks among variables from their observed data has been a popular research topic. We propose a synthetic method, named small-shuffle partial symbolic transfer entropy spectrum (SSPSTES), for inferring association network from multivariate time series. The method synthesizes surrogate data, partial symbolic transfer entropy (PSTE) and Granger causality. A proper threshold selection is crucial for common correlation identification methods and it is not easy for users. The proposed method can not only identify the strong correlation without selecting a threshold but also has the ability of correlation quantification, direction identification and temporal relation identification. The method can be divided into three layers, i.e. data layer, model layer and network layer. In the model layer, the method identifies all the possible pair-wise correlation. In the network layer, we introduce a filter algorithm to remove the indirect weak correlation and retain strong correlation. Finally, we build a weighted adjacency matrix, the value of each entry representing the correlation level between pair-wise variables, and then get the weighted directed association network. Two numerical simulated data from linear system and nonlinear system are illustrated to show the steps and performance of the proposed approach. The ability of the proposed method is approved by an application finally. PMID:27832153
Uncovering and Managing the Impact of Methodological Choices for the Computational Construction of Socio-Technical Networks from Texts

DTIC Science & Technology

2012-01-01

networks has become fast , cheap, and easy (Shapiro, 1971; Trigg & Weiser, 1986). Modern information and communication technologies, such as the internet...However, once the model is learned, inference time is not subject to this constraint. Therefore, applying the model in end-user applications is fast ...products that facilitate the fast collection and assessment of these networks. For the purpose of analyzing socio-technical networks of geopolitical
A decision network account of reasoning about other people's choices.

PubMed

Jern, Alan; Kemp, Charles

2015-09-01

The ability to predict and reason about other people's choices is fundamental to social interaction. We propose that people reason about other people's choices using mental models that are similar to decision networks. Decision networks are extensions of Bayesian networks that incorporate the idea that choices are made in order to achieve goals. In our first experiment, we explore how people predict the choices of others. Our remaining three experiments explore how people infer the goals and knowledge of others by observing the choices that they make. We show that decision networks account for our data better than alternative computational accounts that do not incorporate the notion of goal-directed choice or that do not rely on probabilistic inference. Copyright © 2015 Elsevier B.V. All rights reserved.
Inference of gene regulatory networks from genome-wide knockout fitness data

PubMed Central

Wang, Liming; Wang, Xiaodong; Arkin, Adam P.; Samoilov, Michael S.

2013-01-01

Motivation: Genome-wide fitness is an emerging type of high-throughput biological data generated for individual organisms by creating libraries of knockouts, subjecting them to broad ranges of environmental conditions, and measuring the resulting clone-specific fitnesses. Since fitness is an organism-scale measure of gene regulatory network behaviour, it may offer certain advantages when insights into such phenotypical and functional features are of primary interest over individual gene expression. Previous works have shown that genome-wide fitness data can be used to uncover novel gene regulatory interactions, when compared with results of more conventional gene expression analysis. Yet, to date, few algorithms have been proposed for systematically using genome-wide mutant fitness data for gene regulatory network inference. Results: In this article, we describe a model and propose an inference algorithm for using fitness data from knockout libraries to identify underlying gene regulatory networks. Unlike most prior methods, the presented approach captures not only structural, but also dynamical and non-linear nature of biomolecular systems involved. A state–space model with non-linear basis is used for dynamically describing gene regulatory networks. Network structure is then elucidated by estimating unknown model parameters. Unscented Kalman filter is used to cope with the non-linearities introduced in the model, which also enables the algorithm to run in on-line mode for practical use. Here, we demonstrate that the algorithm provides satisfying results for both synthetic data as well as empirical measurements of GAL network in yeast Saccharomyces cerevisiae and TyrR–LiuR network in bacteria Shewanella oneidensis. Availability: MATLAB code and datasets are available to download at http://www.duke.edu/∼lw174/Fitness.zip and http://genomics.lbl.gov/supplemental/fitness-bioinf/ Contact: wangx@ee.columbia.edu or mssamoilov@lbl.gov Supplementary information: Supplementary data are available at Bioinformatics online PMID:23271269
A novel prosodic-information synthesizer based on recurrent fuzzy neural network for the Chinese TTS system.

PubMed

Lin, Chin-Teng; Wu, Rui-Cheng; Chang, Jyh-Yeong; Liang, Sheng-Fu

2004-02-01

In this paper, a new technique for the Chinese text-to-speech (TTS) system is proposed. Our major effort focuses on the prosodic information generation. New methodologies for constructing fuzzy rules in a prosodic model simulating human's pronouncing rules are developed. The proposed Recurrent Fuzzy Neural Network (RFNN) is a multilayer recurrent neural network (RNN) which integrates a Self-cOnstructing Neural Fuzzy Inference Network (SONFIN) into a recurrent connectionist structure. The RFNN can be functionally divided into two parts. The first part adopts the SONFIN as a prosodic model to explore the relationship between high-level linguistic features and prosodic information based on fuzzy inference rules. As compared to conventional neural networks, the SONFIN can always construct itself with an economic network size in high learning speed. The second part employs a five-layer network to generate all prosodic parameters by directly using the prosodic fuzzy rules inferred from the first part as well as other important features of syllables. The TTS system combined with the proposed method can behave not only sandhi rules but also the other prosodic phenomena existing in the traditional TTS systems. Moreover, the proposed scheme can even find out some new rules about prosodic phrase structure. The performance of the proposed RFNN-based prosodic model is verified by imbedding it into a Chinese TTS system with a Chinese monosyllable database based on the time-domain pitch synchronous overlap add (TD-PSOLA) method. Our experimental results show that the proposed RFNN can generate proper prosodic parameters including pitch means, pitch shapes, maximum energy levels, syllable duration, and pause duration. Some synthetic sounds are online available for demonstration.
A Dynamic Bayesian Network Based Structural Learning towards Automated Handwritten Digit Recognition

NASA Astrophysics Data System (ADS)

Pauplin, Olivier; Jiang, Jianmin

Pattern recognition using Dynamic Bayesian Networks (DBNs) is currently a growing area of study. In this paper, we present DBN models trained for classification of handwritten digit characters. The structure of these models is partly inferred from the training data of each class of digit before performing parameter learning. Classification results are presented for the four described models.
Inferring genetic interactions via a nonlinear model and an optimization algorithm.

PubMed

Chen, Chung-Ming; Lee, Chih; Chuang, Cheng-Long; Wang, Chia-Chang; Shieh, Grace S

2010-02-26

Biochemical pathways are gradually becoming recognized as central to complex human diseases and recently genetic/transcriptional interactions have been shown to be able to predict partial pathways. With the abundant information made available by microarray gene expression data (MGED), nonlinear modeling of these interactions is now feasible. Two of the latest advances in nonlinear modeling used sigmoid models to depict transcriptional interaction of a transcription factor (TF) for a target gene, but do not model cooperative or competitive interactions of several TFs for a target. An S-shape model and an optimization algorithm (GASA) were developed to infer genetic interactions/transcriptional regulation of several genes simultaneously using MGED. GASA consists of a genetic algorithm (GA) and a simulated annealing (SA) algorithm, which is enhanced by a steepest gradient descent algorithm to avoid being trapped in local minimum. Using simulated data with various degrees of noise, we studied how GASA with two model selection criteria and two search spaces performed. Furthermore, GASA was shown to outperform network component analysis, the time series network inference algorithm (TSNI), GA with regular GA (GAGA) and GA with regular SA. Two applications are demonstrated. First, GASA is applied to infer a subnetwork of human T-cell apoptosis. Several of the predicted interactions are supported by the literature. Second, GASA was applied to infer the transcriptional factors of 34 cell cycle regulated targets in S. cerevisiae, and GASA performed better than one of the latest advances in nonlinear modeling, GAGA and TSNI. Moreover, GASA is able to predict multiple transcription factors for certain targets, and these results coincide with experiments confirmed data in YEASTRACT. GASA is shown to infer both genetic interactions and transcriptional regulatory interactions well. In particular, GASA seems able to characterize the nonlinear mechanism of transcriptional regulatory interactions (TIs) in yeast, and may be applied to infer TIs in other organisms. The predicted genetic interactions of a subnetwork of human T-cell apoptosis coincide with existing partial pathways, suggesting the potential of GASA on inferring biochemical pathways.
LASSIM-A network inference toolbox for genome-wide mechanistic modeling.

PubMed

Magnusson, Rasmus; Mariotti, Guido Pio; Köpsén, Mattias; Lövfors, William; Gawel, Danuta R; Jörnsten, Rebecka; Linde, Jörg; Nordling, Torbjörn E M; Nyman, Elin; Schulze, Sylvie; Nestor, Colm E; Zhang, Huan; Cedersund, Gunnar; Benson, Mikael; Tjärnberg, Andreas; Gustafsson, Mika

2017-06-01

Recent technological advancements have made time-resolved, quantitative, multi-omics data available for many model systems, which could be integrated for systems pharmacokinetic use. Here, we present large-scale simulation modeling (LASSIM), which is a novel mathematical tool for performing large-scale inference using mechanistically defined ordinary differential equations (ODE) for gene regulatory networks (GRNs). LASSIM integrates structural knowledge about regulatory interactions and non-linear equations with multiple steady state and dynamic response expression datasets. The rationale behind LASSIM is that biological GRNs can be simplified using a limited subset of core genes that are assumed to regulate all other gene transcription events in the network. The LASSIM method is implemented as a general-purpose toolbox using the PyGMO Python package to make the most of multicore computers and high performance clusters, and is available at https://gitlab.com/Gustafsson-lab/lassim. As a method, LASSIM works in two steps, where it first infers a non-linear ODE system of the pre-specified core gene expression. Second, LASSIM in parallel optimizes the parameters that model the regulation of peripheral genes by core system genes. We showed the usefulness of this method by applying LASSIM to infer a large-scale non-linear model of naïve Th2 cell differentiation, made possible by integrating Th2 specific bindings, time-series together with six public and six novel siRNA-mediated knock-down experiments. ChIP-seq showed significant overlap for all tested transcription factors. Next, we performed novel time-series measurements of total T-cells during differentiation towards Th2 and verified that our LASSIM model could monitor those data significantly better than comparable models that used the same Th2 bindings. In summary, the LASSIM toolbox opens the door to a new type of model-based data analysis that combines the strengths of reliable mechanistic models with truly systems-level data. We demonstrate the power of this approach by inferring a mechanistically motivated, genome-wide model of the Th2 transcription regulatory system, which plays an important role in several immune related diseases.

F-MAP: A Bayesian approach to infer the gene regulatory network using external hints

PubMed Central

Shahdoust, Maryam; Mahjub, Hossein; Sadeghi, Mehdi

2017-01-01

The Common topological features of related species gene regulatory networks suggest reconstruction of the network of one species by using the further information from gene expressions profile of related species. We present an algorithm to reconstruct the gene regulatory network named; F-MAP, which applies the knowledge about gene interactions from related species. Our algorithm sets a Bayesian framework to estimate the precision matrix of one species microarray gene expressions dataset to infer the Gaussian Graphical model of the network. The conjugate Wishart prior is used and the information from related species is applied to estimate the hyperparameters of the prior distribution by using the factor analysis. Applying the proposed algorithm on six related species of drosophila shows that the precision of reconstructed networks is improved considerably compared to the precision of networks constructed by other Bayesian approaches. PMID:28938012
Data-driven reverse engineering of signaling pathways using ensembles of dynamic models.

PubMed

Henriques, David; Villaverde, Alejandro F; Rocha, Miguel; Saez-Rodriguez, Julio; Banga, Julio R

2017-02-01

Despite significant efforts and remarkable progress, the inference of signaling networks from experimental data remains very challenging. The problem is particularly difficult when the objective is to obtain a dynamic model capable of predicting the effect of novel perturbations not considered during model training. The problem is ill-posed due to the nonlinear nature of these systems, the fact that only a fraction of the involved proteins and their post-translational modifications can be measured, and limitations on the technologies used for growing cells in vitro, perturbing them, and measuring their variations. As a consequence, there is a pervasive lack of identifiability. To overcome these issues, we present a methodology called SELDOM (enSEmbLe of Dynamic lOgic-based Models), which builds an ensemble of logic-based dynamic models, trains them to experimental data, and combines their individual simulations into an ensemble prediction. It also includes a model reduction step to prune spurious interactions and mitigate overfitting. SELDOM is a data-driven method, in the sense that it does not require any prior knowledge of the system: the interaction networks that act as scaffolds for the dynamic models are inferred from data using mutual information. We have tested SELDOM on a number of experimental and in silico signal transduction case-studies, including the recent HPN-DREAM breast cancer challenge. We found that its performance is highly competitive compared to state-of-the-art methods for the purpose of recovering network topology. More importantly, the utility of SELDOM goes beyond basic network inference (i.e. uncovering static interaction networks): it builds dynamic (based on ordinary differential equation) models, which can be used for mechanistic interpretations and reliable dynamic predictions in new experimental conditions (i.e. not used in the training). For this task, SELDOM's ensemble prediction is not only consistently better than predictions from individual models, but also often outperforms the state of the art represented by the methods used in the HPN-DREAM challenge.
Data-driven reverse engineering of signaling pathways using ensembles of dynamic models

PubMed Central

Henriques, David; Villaverde, Alejandro F.; Banga, Julio R.

2017-01-01

Despite significant efforts and remarkable progress, the inference of signaling networks from experimental data remains very challenging. The problem is particularly difficult when the objective is to obtain a dynamic model capable of predicting the effect of novel perturbations not considered during model training. The problem is ill-posed due to the nonlinear nature of these systems, the fact that only a fraction of the involved proteins and their post-translational modifications can be measured, and limitations on the technologies used for growing cells in vitro, perturbing them, and measuring their variations. As a consequence, there is a pervasive lack of identifiability. To overcome these issues, we present a methodology called SELDOM (enSEmbLe of Dynamic lOgic-based Models), which builds an ensemble of logic-based dynamic models, trains them to experimental data, and combines their individual simulations into an ensemble prediction. It also includes a model reduction step to prune spurious interactions and mitigate overfitting. SELDOM is a data-driven method, in the sense that it does not require any prior knowledge of the system: the interaction networks that act as scaffolds for the dynamic models are inferred from data using mutual information. We have tested SELDOM on a number of experimental and in silico signal transduction case-studies, including the recent HPN-DREAM breast cancer challenge. We found that its performance is highly competitive compared to state-of-the-art methods for the purpose of recovering network topology. More importantly, the utility of SELDOM goes beyond basic network inference (i.e. uncovering static interaction networks): it builds dynamic (based on ordinary differential equation) models, which can be used for mechanistic interpretations and reliable dynamic predictions in new experimental conditions (i.e. not used in the training). For this task, SELDOM’s ensemble prediction is not only consistently better than predictions from individual models, but also often outperforms the state of the art represented by the methods used in the HPN-DREAM challenge. PMID:28166222
Inference of RhoGAP/GTPase regulation using single-cell morphological data from a combinatorial RNAi screen.

PubMed

Nir, Oaz; Bakal, Chris; Perrimon, Norbert; Berger, Bonnie

2010-03-01

Biological networks are highly complex systems, consisting largely of enzymes that act as molecular switches to activate/inhibit downstream targets via post-translational modification. Computational techniques have been developed to perform signaling network inference using some high-throughput data sources, such as those generated from transcriptional and proteomic studies, but comparable methods have not been developed to use high-content morphological data, which are emerging principally from large-scale RNAi screens, to these ends. Here, we describe a systematic computational framework based on a classification model for identifying genetic interactions using high-dimensional single-cell morphological data from genetic screens, apply it to RhoGAP/GTPase regulation in Drosophila, and evaluate its efficacy. Augmented by knowledge of the basic structure of RhoGAP/GTPase signaling, namely, that GAPs act directly upstream of GTPases, we apply our framework for identifying genetic interactions to predict signaling relationships between these proteins. We find that our method makes mediocre predictions using only RhoGAP single-knockdown morphological data, yet achieves vastly improved accuracy by including original data from a double-knockdown RhoGAP genetic screen, which likely reflects the redundant network structure of RhoGAP/GTPase signaling. We consider other possible methods for inference and show that our primary model outperforms the alternatives. This work demonstrates the fundamental fact that high-throughput morphological data can be used in a systematic, successful fashion to identify genetic interactions and, using additional elementary knowledge of network structure, to infer signaling relations.
Stochastic inference with spiking neurons in the high-conductance state

NASA Astrophysics Data System (ADS)

Petrovici, Mihai A.; Bill, Johannes; Bytschok, Ilja; Schemmel, Johannes; Meier, Karlheinz

2016-10-01

The highly variable dynamics of neocortical circuits observed in vivo have been hypothesized to represent a signature of ongoing stochastic inference but stand in apparent contrast to the deterministic response of neurons measured in vitro. Based on a propagation of the membrane autocorrelation across spike bursts, we provide an analytical derivation of the neural activation function that holds for a large parameter space, including the high-conductance state. On this basis, we show how an ensemble of leaky integrate-and-fire neurons with conductance-based synapses embedded in a spiking environment can attain the correct firing statistics for sampling from a well-defined target distribution. For recurrent networks, we examine convergence toward stationarity in computer simulations and demonstrate sample-based Bayesian inference in a mixed graphical model. This points to a new computational role of high-conductance states and establishes a rigorous link between deterministic neuron models and functional stochastic dynamics on the network level.
Modeling Psychological Attributes in Psychology – An Epistemological Discussion: Network Analysis vs. Latent Variables

PubMed Central

Guyon, Hervé; Falissard, Bruno; Kop, Jean-Luc

2017-01-01

Network Analysis is considered as a new method that challenges Latent Variable models in inferring psychological attributes. With Network Analysis, psychological attributes are derived from a complex system of components without the need to call on any latent variables. But the ontological status of psychological attributes is not adequately defined with Network Analysis, because a psychological attribute is both a complex system and a property emerging from this complex system. The aim of this article is to reappraise the legitimacy of latent variable models by engaging in an ontological and epistemological discussion on psychological attributes. Psychological attributes relate to the mental equilibrium of individuals embedded in their social interactions, as robust attractors within complex dynamic processes with emergent properties, distinct from physical entities located in precise areas of the brain. Latent variables thus possess legitimacy, because the emergent properties can be conceptualized and analyzed on the sole basis of their manifestations, without exploring the upstream complex system. However, in opposition with the usual Latent Variable models, this article is in favor of the integration of a dynamic system of manifestations. Latent Variables models and Network Analysis thus appear as complementary approaches. New approaches combining Latent Network Models and Network Residuals are certainly a promising new way to infer psychological attributes, placing psychological attributes in an inter-subjective dynamic approach. Pragmatism-realism appears as the epistemological framework required if we are to use latent variables as representations of psychological attributes. PMID:28572780
Scalable Probabilistic Inference for Global Seismic Monitoring

NASA Astrophysics Data System (ADS)

Arora, N. S.; Dear, T.; Russell, S.

2011-12-01

We describe a probabilistic generative model for seismic events, their transmission through the earth, and their detection (or mis-detection) at seismic stations. We also describe an inference algorithm that constructs the most probable event bulletin explaining the observed set of detections. The model and inference are called NET-VISA (network processing vertically integrated seismic analysis) and is designed to replace the current automated network processing at the IDC, the SEL3 bulletin. Our results (attached table) demonstrate that NET-VISA significantly outperforms SEL3 by reducing the missed events from 30.3% down to 12.5%. The difference is even more dramatic for smaller magnitude events. NET-VISA has no difficulty in locating nuclear explosions as well. The attached figure demonstrates the location predicted by NET-VISA versus other bulletins for the second DPRK event. Further evaluation on dense regional networks demonstrates that NET-VISA finds many events missed in the LEB bulletin, which is produced by the human analysts. Large aftershock sequences, as produced by the 2004 December Sumatra earthquake and the 2011 March Tohoku earthquake, can pose a significant load for automated processing, often delaying the IDC bulletins by weeks or months. Indeed these sequences can overload the serial NET-VISA inference as well. We describe an enhancement to NET-VISA to make it multi-threaded, and hence take full advantage of the processing power of multi-core and -cpu machines. Our experiments show that the new inference algorithm is able to achieve 80% efficiency in parallel speedup.
Effective network inference through multivariate information transfer estimation

NASA Astrophysics Data System (ADS)

Dahlqvist, Carl-Henrik; Gnabo, Jean-Yves

2018-06-01

Network representation has steadily gained in popularity over the past decades. In many disciplines such as finance, genetics, neuroscience or human travel to cite a few, the network may not directly be observable and needs to be inferred from time-series data, leading to the issue of separating direct interactions between two entities forming the network from indirect interactions coming through its remaining part. Drawing on recent contributions proposing strategies to deal with this problem such as the so-called "global silencing" approach of Barzel and Barabasi or "network deconvolution" of Feizi et al. (2013), we propose a novel methodology to infer an effective network structure from multivariate conditional information transfers. Its core principal is to test the information transfer between two nodes through a step-wise approach by conditioning the transfer for each pair on a specific set of relevant nodes as identified by our algorithm from the rest of the network. The methodology is model free and can be applied to high-dimensional networks with both inter-lag and intra-lag relationships. It outperforms state-of-the-art approaches for eliminating the redundancies and more generally retrieving simulated artificial networks in our Monte-Carlo experiments. We apply the method to stock market data at different frequencies (15 min, 1 h, 1 day) to retrieve the network of US largest financial institutions and then document how bank's centrality measurements relate to bank's systemic vulnerability.
Perturbation Biology: Inferring Signaling Networks in Cellular Systems

PubMed Central

Miller, Martin L.; Gauthier, Nicholas P.; Jing, Xiaohong; Kaushik, Poorvi; He, Qin; Mills, Gordon; Solit, David B.; Pratilas, Christine A.; Weigt, Martin; Braunstein, Alfredo; Pagnani, Andrea; Zecchina, Riccardo; Sander, Chris

2013-01-01

We present a powerful experimental-computational technology for inferring network models that predict the response of cells to perturbations, and that may be useful in the design of combinatorial therapy against cancer. The experiments are systematic series of perturbations of cancer cell lines by targeted drugs, singly or in combination. The response to perturbation is quantified in terms of relative changes in the measured levels of proteins, phospho-proteins and cellular phenotypes such as viability. Computational network models are derived de novo, i.e., without prior knowledge of signaling pathways, and are based on simple non-linear differential equations. The prohibitively large solution space of all possible network models is explored efficiently using a probabilistic algorithm, Belief Propagation (BP), which is three orders of magnitude faster than standard Monte Carlo methods. Explicit executable models are derived for a set of perturbation experiments in SKMEL-133 melanoma cell lines, which are resistant to the therapeutically important inhibitor of RAF kinase. The resulting network models reproduce and extend known pathway biology. They empower potential discoveries of new molecular interactions and predict efficacious novel drug perturbations, such as the inhibition of PLK1, which is verified experimentally. This technology is suitable for application to larger systems in diverse areas of molecular biology. PMID:24367245
Likelihoods for fixed rank nomination networks

PubMed Central

HOFF, PETER; FOSDICK, BAILEY; VOLFOVSKY, ALEX; STOVEL, KATHERINE

2014-01-01

Many studies that gather social network data use survey methods that lead to censored, missing, or otherwise incomplete information. For example, the popular fixed rank nomination (FRN) scheme, often used in studies of schools and businesses, asks study participants to nominate and rank at most a small number of contacts or friends, leaving the existence of other relations uncertain. However, most statistical models are formulated in terms of completely observed binary networks. Statistical analyses of FRN data with such models ignore the censored and ranked nature of the data and could potentially result in misleading statistical inference. To investigate this possibility, we compare Bayesian parameter estimates obtained from a likelihood for complete binary networks with those obtained from likelihoods that are derived from the FRN scheme, and therefore accommodate the ranked and censored nature of the data. We show analytically and via simulation that the binary likelihood can provide misleading inference, particularly for certain model parameters that relate network ties to characteristics of individuals and pairs of individuals. We also compare these different likelihoods in a data analysis of several adolescent social networks. For some of these networks, the parameter estimates from the binary and FRN likelihoods lead to different conclusions, indicating the importance of analyzing FRN data with a method that accounts for the FRN survey design. PMID:25110586
Mining Gene Regulatory Networks by Neural Modeling of Expression Time-Series.

PubMed

Rubiolo, Mariano; Milone, Diego H; Stegmayer, Georgina

2015-01-01

Discovering gene regulatory networks from data is one of the most studied topics in recent years. Neural networks can be successfully used to infer an underlying gene network by modeling expression profiles as times series. This work proposes a novel method based on a pool of neural networks for obtaining a gene regulatory network from a gene expression dataset. They are used for modeling each possible interaction between pairs of genes in the dataset, and a set of mining rules is applied to accurately detect the subjacent relations among genes. The results obtained on artificial and real datasets confirm the method effectiveness for discovering regulatory networks from a proper modeling of the temporal dynamics of gene expression profiles.
Representing Micro-Macro Linkages by Actor-Based Dynamic Network Models

PubMed Central

Snijders, Tom A.B.; Steglich, Christian E.G.

2014-01-01

Stochastic actor-based models for network dynamics have the primary aim of statistical inference about processes of network change, but may be regarded as a kind of agent-based models. Similar to many other agent-based models, they are based on local rules for actor behavior. Different from many other agent-based models, by including elements of generalized linear statistical models they aim to be realistic detailed representations of network dynamics in empirical data sets. Statistical parallels to micro-macro considerations can be found in the estimation of parameters determining local actor behavior from empirical data, and the assessment of goodness of fit from the correspondence with network-level descriptives. This article studies several network-level consequences of dynamic actor-based models applied to represent cross-sectional network data. Two examples illustrate how network-level characteristics can be obtained as emergent features implied by micro-specifications of actor-based models. PMID:25960578
From Blickets to Synapses: Inferring Temporal Causal Networks by Observation

ERIC Educational Resources Information Center

Fernando, Chrisantha

2013-01-01

How do human infants learn the causal dependencies between events? Evidence suggests that this remarkable feat can be achieved by observation of only a handful of examples. Many computational models have been produced to explain how infants perform causal inference without explicit teaching about statistics or the scientific method. Here, we…
Inferring Phylogenetic Networks Using PhyloNet.

PubMed

Wen, Dingqiao; Yu, Yun; Zhu, Jiafan; Nakhleh, Luay

2018-07-01

PhyloNet was released in 2008 as a software package for representing and analyzing phylogenetic networks. At the time of its release, the main functionalities in PhyloNet consisted of measures for comparing network topologies and a single heuristic for reconciling gene trees with a species tree. Since then, PhyloNet has grown significantly. The software package now includes a wide array of methods for inferring phylogenetic networks from data sets of unlinked loci while accounting for both reticulation (e.g., hybridization) and incomplete lineage sorting. In particular, PhyloNet now allows for maximum parsimony, maximum likelihood, and Bayesian inference of phylogenetic networks from gene tree estimates. Furthermore, Bayesian inference directly from sequence data (sequence alignments or biallelic markers) is implemented. Maximum parsimony is based on an extension of the "minimizing deep coalescences" criterion to phylogenetic networks, whereas maximum likelihood and Bayesian inference are based on the multispecies network coalescent. All methods allow for multiple individuals per species. As computing the likelihood of a phylogenetic network is computationally hard, PhyloNet allows for evaluation and inference of networks using a pseudolikelihood measure. PhyloNet summarizes the results of the various analyzes and generates phylogenetic networks in the extended Newick format that is readily viewable by existing visualization software.
Approximation and inference methods for stochastic biochemical kinetics—a tutorial review

NASA Astrophysics Data System (ADS)

Schnoerr, David; Sanguinetti, Guido; Grima, Ramon

2017-03-01

Stochastic fluctuations of molecule numbers are ubiquitous in biological systems. Important examples include gene expression and enzymatic processes in living cells. Such systems are typically modelled as chemical reaction networks whose dynamics are governed by the chemical master equation. Despite its simple structure, no analytic solutions to the chemical master equation are known for most systems. Moreover, stochastic simulations are computationally expensive, making systematic analysis and statistical inference a challenging task. Consequently, significant effort has been spent in recent decades on the development of efficient approximation and inference methods. This article gives an introduction to basic modelling concepts as well as an overview of state of the art methods. First, we motivate and introduce deterministic and stochastic methods for modelling chemical networks, and give an overview of simulation and exact solution methods. Next, we discuss several approximation methods, including the chemical Langevin equation, the system size expansion, moment closure approximations, time-scale separation approximations and hybrid methods. We discuss their various properties and review recent advances and remaining challenges for these methods. We present a comparison of several of these methods by means of a numerical case study and highlight some of their respective advantages and disadvantages. Finally, we discuss the problem of inference from experimental data in the Bayesian framework and review recent methods developed the literature. In summary, this review gives a self-contained introduction to modelling, approximations and inference methods for stochastic chemical kinetics.
Inference of time-delayed gene regulatory networks based on dynamic Bayesian network hybrid learning method

PubMed Central

Yu, Bin; Xu, Jia-Meng; Li, Shan; Chen, Cheng; Chen, Rui-Xin; Wang, Lei; Zhang, Yan; Wang, Ming-Hui

2017-01-01

Gene regulatory networks (GRNs) research reveals complex life phenomena from the perspective of gene interaction, which is an important research field in systems biology. Traditional Bayesian networks have a high computational complexity, and the network structure scoring model has a single feature. Information-based approaches cannot identify the direction of regulation. In order to make up for the shortcomings of the above methods, this paper presents a novel hybrid learning method (DBNCS) based on dynamic Bayesian network (DBN) to construct the multiple time-delayed GRNs for the first time, combining the comprehensive score (CS) with the DBN model. DBNCS algorithm first uses CMI2NI (conditional mutual inclusive information-based network inference) algorithm for network structure profiles learning, namely the construction of search space. Then the redundant regulations are removed by using the recursive optimization algorithm (RO), thereby reduce the false positive rate. Secondly, the network structure profiles are decomposed into a set of cliques without loss, which can significantly reduce the computational complexity. Finally, DBN model is used to identify the direction of gene regulation within the cliques and search for the optimal network structure. The performance of DBNCS algorithm is evaluated by the benchmark GRN datasets from DREAM challenge as well as the SOS DNA repair network in Escherichia coli, and compared with other state-of-the-art methods. The experimental results show the rationality of the algorithm design and the outstanding performance of the GRNs. PMID:29113310
Inference of time-delayed gene regulatory networks based on dynamic Bayesian network hybrid learning method.

PubMed

Yu, Bin; Xu, Jia-Meng; Li, Shan; Chen, Cheng; Chen, Rui-Xin; Wang, Lei; Zhang, Yan; Wang, Ming-Hui

2017-10-06

Gene regulatory networks (GRNs) research reveals complex life phenomena from the perspective of gene interaction, which is an important research field in systems biology. Traditional Bayesian networks have a high computational complexity, and the network structure scoring model has a single feature. Information-based approaches cannot identify the direction of regulation. In order to make up for the shortcomings of the above methods, this paper presents a novel hybrid learning method (DBNCS) based on dynamic Bayesian network (DBN) to construct the multiple time-delayed GRNs for the first time, combining the comprehensive score (CS) with the DBN model. DBNCS algorithm first uses CMI2NI (conditional mutual inclusive information-based network inference) algorithm for network structure profiles learning, namely the construction of search space. Then the redundant regulations are removed by using the recursive optimization algorithm (RO), thereby reduce the false positive rate. Secondly, the network structure profiles are decomposed into a set of cliques without loss, which can significantly reduce the computational complexity. Finally, DBN model is used to identify the direction of gene regulation within the cliques and search for the optimal network structure. The performance of DBNCS algorithm is evaluated by the benchmark GRN datasets from DREAM challenge as well as the SOS DNA repair network in Escherichia coli , and compared with other state-of-the-art methods. The experimental results show the rationality of the algorithm design and the outstanding performance of the GRNs.
Discovering time-lagged rules from microarray data using gene profile classifiers

PubMed Central

2011-01-01

Background Gene regulatory networks have an essential role in every process of life. In this regard, the amount of genome-wide time series data is becoming increasingly available, providing the opportunity to discover the time-delayed gene regulatory networks that govern the majority of these molecular processes. Results This paper aims at reconstructing gene regulatory networks from multiple genome-wide microarray time series datasets. In this sense, a new model-free algorithm called GRNCOP2 (Gene Regulatory Network inference by Combinatorial OPtimization 2), which is a significant evolution of the GRNCOP algorithm, was developed using combinatorial optimization of gene profile classifiers. The method is capable of inferring potential time-delay relationships with any span of time between genes from various time series datasets given as input. The proposed algorithm was applied to time series data composed of twenty yeast genes that are highly relevant for the cell-cycle study, and the results were compared against several related approaches. The outcomes have shown that GRNCOP2 outperforms the contrasted methods in terms of the proposed metrics, and that the results are consistent with previous biological knowledge. Additionally, a genome-wide study on multiple publicly available time series data was performed. In this case, the experimentation has exhibited the soundness and scalability of the new method which inferred highly-related statistically-significant gene associations. Conclusions A novel method for inferring time-delayed gene regulatory networks from genome-wide time series datasets is proposed in this paper. The method was carefully validated with several publicly available data sets. The results have demonstrated that the algorithm constitutes a usable model-free approach capable of predicting meaningful relationships between genes, revealing the time-trends of gene regulation. PMID:21524308
Multinomial Bayesian learning for modeling classical and nonclassical receptive field properties.

PubMed

Hosoya, Haruo

2012-08-01

We study the interplay of Bayesian inference and natural image learning in a hierarchical vision system, in relation to the response properties of early visual cortex. We particularly focus on a Bayesian network with multinomial variables that can represent discrete feature spaces similar to hypercolumns combining minicolumns, enforce sparsity of activation to learn efficient representations, and explain divisive normalization. We demonstrate that maximal-likelihood learning using sampling-based Bayesian inference gives rise to classical receptive field properties similar to V1 simple cells and V2 cells, while inference performed on the trained network yields nonclassical context-dependent response properties such as cross-orientation suppression and filling in. Comparison with known physiological properties reveals some qualitative and quantitative similarities.
Combining epidemiological and genetic networks signifies the importance of early treatment in HIV-1 transmission.

PubMed

Zarrabi, Narges; Prosperi, Mattia; Belleman, Robert G; Colafigli, Manuela; De Luca, Andrea; Sloot, Peter M A

2012-01-01

Inferring disease transmission networks is important in epidemiology in order to understand and prevent the spread of infectious diseases. Reconstruction of the infection transmission networks requires insight into viral genome data as well as social interactions. For the HIV-1 epidemic, current research either uses genetic information of patients' virus to infer the past infection events or uses statistics of sexual interactions to model the network structure of viral spreading. Methods for a reliable reconstruction of HIV-1 transmission dynamics, taking into account both molecular and societal data are still lacking. The aim of this study is to combine information from both genetic and epidemiological scales to characterize and analyse a transmission network of the HIV-1 epidemic in central Italy.We introduce a novel filter-reduction method to build a network of HIV infected patients based on their social and treatment information. The network is then combined with a genetic network, to infer a hypothetical infection transmission network. We apply this method to a cohort study of HIV-1 infected patients in central Italy and find that patients who are highly connected in the network have longer untreated infection periods. We also find that the network structures for homosexual males and heterosexual populations are heterogeneous, consisting of a majority of 'peripheral nodes' that have only a few sexual interactions and a minority of 'hub nodes' that have many sexual interactions. Inferring HIV-1 transmission networks using this novel combined approach reveals remarkable correlations between high out-degree individuals and longer untreated infection periods. These findings signify the importance of early treatment and support the potential benefit of wide population screening, management of early diagnoses and anticipated antiretroviral treatment to prevent viral transmission and spread. The approach presented here for reconstructing HIV-1 transmission networks can have important repercussions in the design of intervention strategies for disease control.

Efficient Reverse-Engineering of a Developmental Gene Regulatory Network

PubMed Central

Cicin-Sain, Damjan; Ashyraliyev, Maksat; Jaeger, Johannes

2012-01-01

Understanding the complex regulatory networks underlying development and evolution of multi-cellular organisms is a major problem in biology. Computational models can be used as tools to extract the regulatory structure and dynamics of such networks from gene expression data. This approach is called reverse engineering. It has been successfully applied to many gene networks in various biological systems. However, to reconstitute the structure and non-linear dynamics of a developmental gene network in its spatial context remains a considerable challenge. Here, we address this challenge using a case study: the gap gene network involved in segment determination during early development of Drosophila melanogaster. A major problem for reverse-engineering pattern-forming networks is the significant amount of time and effort required to acquire and quantify spatial gene expression data. We have developed a simplified data processing pipeline that considerably increases the throughput of the method, but results in data of reduced accuracy compared to those previously used for gap gene network inference. We demonstrate that we can infer the correct network structure using our reduced data set, and investigate minimal data requirements for successful reverse engineering. Our results show that timing and position of expression domain boundaries are the crucial features for determining regulatory network structure from data, while it is less important to precisely measure expression levels. Based on this, we define minimal data requirements for gap gene network inference. Our results demonstrate the feasibility of reverse-engineering with much reduced experimental effort. This enables more widespread use of the method in different developmental contexts and organisms. Such systematic application of data-driven models to real-world networks has enormous potential. Only the quantitative investigation of a large number of developmental gene regulatory networks will allow us to discover whether there are rules or regularities governing development and evolution of complex multi-cellular organisms. PMID:22807664
Ensemble methods for stochastic networks with special reference to the biological clock of Neurospora crassa.

PubMed

Caranica, C; Al-Omari, A; Deng, Z; Griffith, J; Nilsen, R; Mao, L; Arnold, J; Schüttler, H-B

2018-01-01

A major challenge in systems biology is to infer the parameters of regulatory networks that operate in a noisy environment, such as in a single cell. In a stochastic regime it is hard to distinguish noise from the real signal and to infer the noise contribution to the dynamical behavior. When the genetic network displays oscillatory dynamics, it is even harder to infer the parameters that produce the oscillations. To address this issue we introduce a new estimation method built on a combination of stochastic simulations, mass action kinetics and ensemble network simulations in which we match the average periodogram and phase of the model to that of the data. The method is relatively fast (compared to Metropolis-Hastings Monte Carlo Methods), easy to parallelize, applicable to large oscillatory networks and large (~2000 cells) single cell expression data sets, and it quantifies the noise impact on the observed dynamics. Standard errors of estimated rate coefficients are typically two orders of magnitude smaller than the mean from single cell experiments with on the order of ~1000 cells. We also provide a method to assess the goodness of fit of the stochastic network using the Hilbert phase of single cells. An analysis of phase departures from the null model with no communication between cells is consistent with a hypothesis of Stochastic Resonance describing single cell oscillators. Stochastic Resonance provides a physical mechanism whereby intracellular noise plays a positive role in establishing oscillatory behavior, but may require model parameters, such as rate coefficients, that differ substantially from those extracted at the macroscopic level from measurements on populations of millions of communicating, synchronized cells.
Neural network modelling of the influence of channelopathies on reflex visual attention.

PubMed

Gravier, Alexandre; Quek, Chai; Duch, Włodzisław; Wahab, Abdul; Gravier-Rymaszewska, Joanna

2016-02-01

This paper introduces a model of Emergent Visual Attention in presence of calcium channelopathy (EVAC). By modelling channelopathy, EVAC constitutes an effort towards identifying the possible causes of autism. The network structure embodies the dual pathways model of cortical processing of visual input, with reflex attention as an emergent property of neural interactions. EVAC extends existing work by introducing attention shift in a larger-scale network and applying a phenomenological model of channelopathy. In presence of a distractor, the channelopathic network's rate of failure to shift attention is lower than the control network's, but overall, the control network exhibits a lower classification error rate. The simulation results also show differences in task-relative reaction times between control and channelopathic networks. The attention shift timings inferred from the model are consistent with studies of attention shift in autistic children.
Emulation of reionization simulations for Bayesian inference of astrophysics parameters using neural networks

NASA Astrophysics Data System (ADS)

Schmit, C. J.; Pritchard, J. R.

2018-03-01

Next generation radio experiments such as LOFAR, HERA, and SKA are expected to probe the Epoch of Reionization (EoR) and claim a first direct detection of the cosmic 21cm signal within the next decade. Data volumes will be enormous and can thus potentially revolutionize our understanding of the early Universe and galaxy formation. However, numerical modelling of the EoR can be prohibitively expensive for Bayesian parameter inference and how to optimally extract information from incoming data is currently unclear. Emulation techniques for fast model evaluations have recently been proposed as a way to bypass costly simulations. We consider the use of artificial neural networks as a blind emulation technique. We study the impact of training duration and training set size on the quality of the network prediction and the resulting best-fitting values of a parameter search. A direct comparison is drawn between our emulation technique and an equivalent analysis using 21CMMC. We find good predictive capabilities of our network using training sets of as low as 100 model evaluations, which is within the capabilities of fully numerical radiative transfer codes.
Functional network inference of the suprachiasmatic nucleus

PubMed Central

Abel, John H.; Meeker, Kirsten; Granados-Fuentes, Daniel; St. John, Peter C.; Wang, Thomas J.; Bales, Benjamin B.; Doyle, Francis J.; Herzog, Erik D.; Petzold, Linda R.

2016-01-01

In the mammalian suprachiasmatic nucleus (SCN), noisy cellular oscillators communicate within a neuronal network to generate precise system-wide circadian rhythms. Although the intracellular genetic oscillator and intercellular biochemical coupling mechanisms have been examined previously, the network topology driving synchronization of the SCN has not been elucidated. This network has been particularly challenging to probe, due to its oscillatory components and slow coupling timescale. In this work, we investigated the SCN network at a single-cell resolution through a chemically induced desynchronization. We then inferred functional connections in the SCN by applying the maximal information coefficient statistic to bioluminescence reporter data from individual neurons while they resynchronized their circadian cycling. Our results demonstrate that the functional network of circadian cells associated with resynchronization has small-world characteristics, with a node degree distribution that is exponential. We show that hubs of this small-world network are preferentially located in the central SCN, with sparsely connected shells surrounding these cores. Finally, we used two computational models of circadian neurons to validate our predictions of network structure. PMID:27044085
High-dimensional inference with the generalized Hopfield model: principal component analysis and corrections.

PubMed

Cocco, S; Monasson, R; Sessak, V

2011-05-01

We consider the problem of inferring the interactions between a set of N binary variables from the knowledge of their frequencies and pairwise correlations. The inference framework is based on the Hopfield model, a special case of the Ising model where the interaction matrix is defined through a set of patterns in the variable space, and is of rank much smaller than N. We show that maximum likelihood inference is deeply related to principal component analysis when the amplitude of the pattern components ξ is negligible compared to √N. Using techniques from statistical mechanics, we calculate the corrections to the patterns to the first order in ξ/√N. We stress the need to generalize the Hopfield model and include both attractive and repulsive patterns in order to correctly infer networks with sparse and strong interactions. We present a simple geometrical criterion to decide how many attractive and repulsive patterns should be considered as a function of the sampling noise. We moreover discuss how many sampled configurations are required for a good inference, as a function of the system size N and of the amplitude ξ. The inference approach is illustrated on synthetic and biological data.
The transmission process: A combinatorial stochastic process for the evolution of transmission trees over networks.

PubMed

Sainudiin, Raazesh; Welch, David

2016-12-07

We derive a combinatorial stochastic process for the evolution of the transmission tree over the infected vertices of a host contact network in a susceptible-infected (SI) model of an epidemic. Models of transmission trees are crucial to understanding the evolution of pathogen populations. We provide an explicit description of the transmission process on the product state space of (rooted planar ranked labelled) binary transmission trees and labelled host contact networks with SI-tags as a discrete-state continuous-time Markov chain. We give the exact probability of any transmission tree when the host contact network is a complete, star or path network - three illustrative examples. We then develop a biparametric Beta-splitting model that directly generates transmission trees with exact probabilities as a function of the model parameters, but without explicitly modelling the underlying contact network, and show that for specific values of the parameters we can recover the exact probabilities for our three example networks through the Markov chain construction that explicitly models the underlying contact network. We use the maximum likelihood estimator (MLE) to consistently infer the two parameters driving the transmission process based on observations of the transmission trees and use the exact MLE to characterize equivalence classes over the space of contact networks with a single initial infection. An exploratory simulation study of the MLEs from transmission trees sampled from three other deterministic and four random families of classical contact networks is conducted to shed light on the relation between the MLEs of these families with some implications for statistical inference along with pointers to further extensions of our models. The insights developed here are also applicable to the simplest models of "meme" evolution in online social media networks through transmission events that can be distilled from observable actions such as "likes", "mentions", "retweets" and "+1s" along with any concomitant comments. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.
Enhancing Transparency and Control When Drawing Data-Driven Inferences About Individuals.

PubMed

Chen, Daizhuo; Fraiberger, Samuel P; Moakler, Robert; Provost, Foster

2017-09-01

Recent studies show the remarkable power of fine-grained information disclosed by users on social network sites to infer users' personal characteristics via predictive modeling. Similar fine-grained data are being used successfully in other commercial applications. In response, attention is turning increasingly to the transparency that organizations provide to users as to what inferences are drawn and why, as well as to what sort of control users can be given over inferences that are drawn about them. In this article, we focus on inferences about personal characteristics based on information disclosed by users' online actions. As a use case, we explore personal inferences that are made possible from "Likes" on Facebook. We first present a means for providing transparency into the information responsible for inferences drawn by data-driven models. We then introduce the "cloaking device"-a mechanism for users to inhibit the use of particular pieces of information in inference. Using these analytical tools we ask two main questions: (1) How much information must users cloak to significantly affect inferences about their personal traits? We find that usually users must cloak only a small portion of their actions to inhibit inference. We also find that, encouragingly, false-positive inferences are significantly easier to cloak than true-positive inferences. (2) Can firms change their modeling behavior to make cloaking more difficult? The answer is a definitive yes. We demonstrate a simple modeling change that requires users to cloak substantially more information to affect the inferences drawn. The upshot is that organizations can provide transparency and control even into complicated, predictive model-driven inferences, but they also can make control easier or harder for their users.
Enhancing Transparency and Control When Drawing Data-Driven Inferences About Individuals

PubMed Central

Chen, Daizhuo; Fraiberger, Samuel P.; Moakler, Robert; Provost, Foster

2017-01-01

Abstract Recent studies show the remarkable power of fine-grained information disclosed by users on social network sites to infer users' personal characteristics via predictive modeling. Similar fine-grained data are being used successfully in other commercial applications. In response, attention is turning increasingly to the transparency that organizations provide to users as to what inferences are drawn and why, as well as to what sort of control users can be given over inferences that are drawn about them. In this article, we focus on inferences about personal characteristics based on information disclosed by users' online actions. As a use case, we explore personal inferences that are made possible from “Likes” on Facebook. We first present a means for providing transparency into the information responsible for inferences drawn by data-driven models. We then introduce the “cloaking device”—a mechanism for users to inhibit the use of particular pieces of information in inference. Using these analytical tools we ask two main questions: (1) How much information must users cloak to significantly affect inferences about their personal traits? We find that usually users must cloak only a small portion of their actions to inhibit inference. We also find that, encouragingly, false-positive inferences are significantly easier to cloak than true-positive inferences. (2) Can firms change their modeling behavior to make cloaking more difficult? The answer is a definitive yes. We demonstrate a simple modeling change that requires users to cloak substantially more information to affect the inferences drawn. The upshot is that organizations can provide transparency and control even into complicated, predictive model-driven inferences, but they also can make control easier or harder for their users. PMID:28933942
Combinatorial influence of environmental parameters on transcription factor activity.

PubMed

Knijnenburg, T A; Wessels, L F A; Reinders, M J T

2008-07-01

Cells receive a wide variety of environmental signals, which are often processed combinatorially to generate specific genetic responses. Changes in transcript levels, as observed across different environmental conditions, can, to a large extent, be attributed to changes in the activity of transcription factors (TFs). However, in unraveling these transcription regulation networks, the actual environmental signals are often not incorporated into the model, simply because they have not been measured. The unquantified heterogeneity of the environmental parameters across microarray experiments frustrates regulatory network inference. We propose an inference algorithm that models the influence of environmental parameters on gene expression. The approach is based on a yeast microarray compendium of chemostat steady-state experiments. Chemostat cultivation enables the accurate control and measurement of many of the key cultivation parameters, such as nutrient concentrations, growth rate and temperature. The observed transcript levels are explained by inferring the activity of TFs in response to combinations of cultivation parameters. The interplay between activated enhancers and repressors that bind a gene promoter determine the possible up- or downregulation of the gene. The model is translated into a linear integer optimization problem. The resulting regulatory network identifies the combinatorial effects of environmental parameters on TF activity and gene expression. The Matlab code is available from the authors upon request. Supplementary data are available at Bioinformatics online.
Bayesian Inference of Natural Rankings in Incomplete Competition Networks

PubMed Central

Park, Juyong; Yook, Soon-Hyung

2014-01-01

Competition between a complex system's constituents and a corresponding reward mechanism based on it have profound influence on the functioning, stability, and evolution of the system. But determining the dominance hierarchy or ranking among the constituent parts from the strongest to the weakest – essential in determining reward and penalty – is frequently an ambiguous task due to the incomplete (partially filled) nature of competition networks. Here we introduce the “Natural Ranking,” an unambiguous ranking method applicable to a round robin tournament, and formulate an analytical model based on the Bayesian formula for inferring the expected mean and error of the natural ranking of nodes from an incomplete network. We investigate its potential and uses in resolving important issues of ranking by applying it to real-world competition networks. PMID:25163528
Bayesian Inference of Natural Rankings in Incomplete Competition Networks

NASA Astrophysics Data System (ADS)

Park, Juyong; Yook, Soon-Hyung

2014-08-01

Competition between a complex system's constituents and a corresponding reward mechanism based on it have profound influence on the functioning, stability, and evolution of the system. But determining the dominance hierarchy or ranking among the constituent parts from the strongest to the weakest - essential in determining reward and penalty - is frequently an ambiguous task due to the incomplete (partially filled) nature of competition networks. Here we introduce the ``Natural Ranking,'' an unambiguous ranking method applicable to a round robin tournament, and formulate an analytical model based on the Bayesian formula for inferring the expected mean and error of the natural ranking of nodes from an incomplete network. We investigate its potential and uses in resolving important issues of ranking by applying it to real-world competition networks.
Inferring microbial interaction networks from metagenomic data using SgLV-EKF algorithm.

PubMed

Alshawaqfeh, Mustafa; Serpedin, Erchin; Younes, Ahmad Bani

2017-03-27

Inferring the microbial interaction networks (MINs) and modeling their dynamics are critical in understanding the mechanisms of the bacterial ecosystem and designing antibiotic and/or probiotic therapies. Recently, several approaches were proposed to infer MINs using the generalized Lotka-Volterra (gLV) model. Main drawbacks of these models include the fact that these models only consider the measurement noise without taking into consideration the uncertainties in the underlying dynamics. Furthermore, inferring the MIN is characterized by the limited number of observations and nonlinearity in the regulatory mechanisms. Therefore, novel estimation techniques are needed to address these challenges. This work proposes SgLV-EKF: a stochastic gLV model that adopts the extended Kalman filter (EKF) algorithm to model the MIN dynamics. In particular, SgLV-EKF employs a stochastic modeling of the MIN by adding a noise term to the dynamical model to compensate for modeling uncertainties. This stochastic modeling is more realistic than the conventional gLV model which assumes that the MIN dynamics are perfectly governed by the gLV equations. After specifying the stochastic model structure, we propose the EKF to estimate the MIN. SgLV-EKF was compared with two similarity-based algorithms, one algorithm from the integral-based family and two regression-based algorithms, in terms of the achieved performance on two synthetic data-sets and two real data-sets. The first data-set models the randomness in measurement data, whereas, the second data-set incorporates uncertainties in the underlying dynamics. The real data-sets are provided by a recent study pertaining to an antibiotic-mediated Clostridium difficile infection. The experimental results demonstrate that SgLV-EKF outperforms the alternative methods in terms of robustness to measurement noise, modeling errors, and tracking the dynamics of the MIN. Performance analysis demonstrates that the proposed SgLV-EKF algorithm represents a powerful and reliable tool to infer MINs and track their dynamics.
Automated adaptive inference of phenomenological dynamical models.

PubMed

Daniels, Bryan C; Nemenman, Ilya

2015-08-21

Dynamics of complex systems is often driven by large and intricate networks of microscopic interactions, whose sheer size obfuscates understanding. With limited experimental data, many parameters of such dynamics are unknown, and thus detailed, mechanistic models risk overfitting and making faulty predictions. At the other extreme, simple ad hoc models often miss defining features of the underlying systems. Here we develop an approach that instead constructs phenomenological, coarse-grained models of network dynamics that automatically adapt their complexity to the available data. Such adaptive models produce accurate predictions even when microscopic details are unknown. The approach is computationally tractable, even for a relatively large number of dynamical variables. Using simulated data, it correctly infers the phase space structure for planetary motion, avoids overfitting in a biological signalling system and produces accurate predictions for yeast glycolysis with tens of data points and over half of the interacting species unobserved.
Automated adaptive inference of phenomenological dynamical models

PubMed Central

Daniels, Bryan C.; Nemenman, Ilya

2015-01-01

Dynamics of complex systems is often driven by large and intricate networks of microscopic interactions, whose sheer size obfuscates understanding. With limited experimental data, many parameters of such dynamics are unknown, and thus detailed, mechanistic models risk overfitting and making faulty predictions. At the other extreme, simple ad hoc models often miss defining features of the underlying systems. Here we develop an approach that instead constructs phenomenological, coarse-grained models of network dynamics that automatically adapt their complexity to the available data. Such adaptive models produce accurate predictions even when microscopic details are unknown. The approach is computationally tractable, even for a relatively large number of dynamical variables. Using simulated data, it correctly infers the phase space structure for planetary motion, avoids overfitting in a biological signalling system and produces accurate predictions for yeast glycolysis with tens of data points and over half of the interacting species unobserved. PMID:26293508
DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Y.C.; Doolen, G.; Chen, H.H.

A high-order correlation tensor formalism for neural networks is described. The model can simulate auto associative, heteroassociative, as well as multiassociative memory. For the autoassociative model, simulation results show a drastic increase in the memory capacity and speed over that of the standard Hopfield-like correlation matrix methods. The possibility of using multiassociative memory for a learning universal inference network is also discussed. 9 refs., 5 figs.
Data-driven inference of network connectivity for modeling the dynamics of neural codes in the insect antennal lobe

PubMed Central

Shlizerman, Eli; Riffell, Jeffrey A.; Kutz, J. Nathan

2014-01-01

The antennal lobe (AL), olfactory processing center in insects, is able to process stimuli into distinct neural activity patterns, called olfactory neural codes. To model their dynamics we perform multichannel recordings from the projection neurons in the AL driven by different odorants. We then derive a dynamic neuronal network from the electrophysiological data. The network consists of lateral-inhibitory neurons and excitatory neurons (modeled as firing-rate units), and is capable of producing unique olfactory neural codes for the tested odorants. To construct the network, we (1) design a projection, an odor space, for the neural recording from the AL, which discriminates between distinct odorants trajectories (2) characterize scent recognition, i.e., decision-making based on olfactory signals and (3) infer the wiring of the neural circuit, the connectome of the AL. We show that the constructed model is consistent with biological observations, such as contrast enhancement and robustness to noise. The study suggests a data-driven approach to answer a key biological question in identifying how lateral inhibitory neurons can be wired to excitatory neurons to permit robust activity patterns. PMID:25165442
What Can Causal Networks Tell Us about Metabolic Pathways?

PubMed Central

Blair, Rachael Hageman; Kliebenstein, Daniel J.; Churchill, Gary A.

2012-01-01

Graphical models describe the linear correlation structure of data and have been used to establish causal relationships among phenotypes in genetic mapping populations. Data are typically collected at a single point in time. Biological processes on the other hand are often non-linear and display time varying dynamics. The extent to which graphical models can recapitulate the architecture of an underlying biological processes is not well understood. We consider metabolic networks with known stoichiometry to address the fundamental question: “What can causal networks tell us about metabolic pathways?”. Using data from an Arabidopsis BaySha population and simulated data from dynamic models of pathway motifs, we assess our ability to reconstruct metabolic pathways using graphical models. Our results highlight the necessity of non-genetic residual biological variation for reliable inference. Recovery of the ordering within a pathway is possible, but should not be expected. Causal inference is sensitive to subtle patterns in the correlation structure that may be driven by a variety of factors, which may not emphasize the substrate-product relationship. We illustrate the effects of metabolic pathway architecture, epistasis and stochastic variation on correlation structure and graphical model-derived networks. We conclude that graphical models should be interpreted cautiously, especially if the implied causal relationships are to be used in the design of intervention strategies. PMID:22496633
Quantum-Like Bayesian Networks for Modeling Decision Making

PubMed Central

Moreira, Catarina; Wichert, Andreas

2016-01-01

In this work, we explore an alternative quantum structure to perform quantum probabilistic inferences to accommodate the paradoxical findings of the Sure Thing Principle. We propose a Quantum-Like Bayesian Network, which consists in replacing classical probabilities by quantum probability amplitudes. However, since this approach suffers from the problem of exponential growth of quantum parameters, we also propose a similarity heuristic that automatically fits quantum parameters through vector similarities. This makes the proposed model general and predictive in contrast to the current state of the art models, which cannot be generalized for more complex decision scenarios and that only provide an explanatory nature for the observed paradoxes. In the end, the model that we propose consists in a nonparametric method for estimating inference effects from a statistical point of view. It is a statistical model that is simpler than the previous quantum dynamic and quantum-like models proposed in the literature. We tested the proposed network with several empirical data from the literature, mainly from the Prisoner's Dilemma game and the Two Stage Gambling game. The results obtained show that the proposed quantum Bayesian Network is a general method that can accommodate violations of the laws of classical probability theory and make accurate predictions regarding human decision-making in these scenarios. PMID:26858669
Statistical comparison of a hybrid approach with approximate and exact inference models for Fusion 2+

NASA Astrophysics Data System (ADS)

Lee, K. David; Wiesenfeld, Eric; Gelfand, Andrew

2007-04-01

One of the greatest challenges in modern combat is maintaining a high level of timely Situational Awareness (SA). In many situations, computational complexity and accuracy considerations make the development and deployment of real-time, high-level inference tools very difficult. An innovative hybrid framework that combines Bayesian inference, in the form of Bayesian Networks, and Possibility Theory, in the form of Fuzzy Logic systems, has recently been introduced to provide a rigorous framework for high-level inference. In previous research, the theoretical basis and benefits of the hybrid approach have been developed. However, lacking is a concrete experimental comparison of the hybrid framework with traditional fusion methods, to demonstrate and quantify this benefit. The goal of this research, therefore, is to provide a statistical analysis on the comparison of the accuracy and performance of hybrid network theory, with pure Bayesian and Fuzzy systems and an inexact Bayesian system approximated using Particle Filtering. To accomplish this task, domain specific models will be developed under these different theoretical approaches and then evaluated, via Monte Carlo Simulation, in comparison to situational ground truth to measure accuracy and fidelity. Following this, a rigorous statistical analysis of the performance results will be performed, to quantify the benefit of hybrid inference to other fusion tools.

Mathematical inference and control of molecular networks from perturbation experiments

NASA Astrophysics Data System (ADS)

Mohammed-Rasheed, Mohammed

One of the main challenges facing biologists and mathematicians in the post genomic era is to understand the behavior of molecular networks and harness this understanding into an educated intervention of the cell. The cell maintains its function via an elaborate network of interconnecting positive and negative feedback loops of genes, RNA and proteins that send different signals to a large number of pathways and molecules. These structures are referred to as genetic regulatory networks (GRNs) or molecular networks. GRNs can be viewed as dynamical systems with inherent properties and mechanisms, such as steady-state equilibriums and stability, that determine the behavior of the cell. The biological relevance of the mathematical concepts are important as they may predict the differentiation of a stem cell, the maintenance of a normal cell, the development of cancer and its aberrant behavior, and the design of drugs and response to therapy. Uncovering the underlying GRN structure from gene/protein expression data, e.g., microarrays or perturbation experiments, is called inference or reverse engineering of the molecular network. Because of the high cost and time consuming nature of biological experiments, the number of available measurements or experiments is very small compared to the number of molecules (genes, RNA and proteins). In addition, the observations are noisy, where the noise is due to the measurements imperfections as well as the inherent stochasticity of genetic expression levels. Intra-cellular activities and extra-cellular environmental attributes are also another source of variability. Thus, the inference of GRNs is, in general, an under-determined problem with a highly noisy set of observations. The ultimate goal of GRN inference and analysis is to be able to intervene within the network, in order to force it away from undesirable cellular states and into desirable ones. However, it remains a major challenge to design optimal intervention strategies in order to affect the time evolution of molecular activity in a desirable manner. In this proposal, we address both the inference and control problems of GRNs. In the first part of the thesis, we consider the control problem. We assume that we are given a general topology network structure, whose dynamics follow a discrete-time Markov chain model. We subsequently develop a comprehensive framework for optimal perturbation control of the network. The aim of the perturbation is to drive the network away from undesirable steady-states and to force it to converge to a unique desirable steady-state. The proposed framework does not make any assumptions about the topology of the initial network (e.g., ergodicity, weak and strong connectivity), and is thus applicable to general topology networks. We define the optimal perturbation as the minimum-energy perturbation measured in terms of the Frobenius norm between the initial and perturbed networks. We subsequently demonstrate that there exists at most one optimal perturbation that forces the network into the desirable steady-state. In the event where the optimal perturbation does not exist, we construct a family of sub-optimal perturbations that approximate the optimal solution arbitrarily closely. In the second part of the thesis, we address the inference problem of GRNs from time series data. We model the dynamics of the molecules using a system of ordinary differential equations corrupted by additive white noise. For large-scale networks, we formulate the inference problem as a constrained maximum likelihood estimation problem. We derive the molecular interactions that maximize the likelihood function while constraining the network to be sparse. We further propose a procedure to recover weak interactions based on the Bayesian information criterion. For small-size networks, we investigated the inference of a globally stable 7-gene melanoma genetic regulatory network from genetic perturbation experiments. We considered five melanoma cell lines, who exhibit different motility/invasion behavior under the same perturbation experiment of gene Wnt5a. The results of the simulations validate both the steady state levels and the experimental data of the perturbation experiments of all five cell lines. The goal of this study is to answer important questions that link the response of the network to perturbations, as measured by the experiments, to its structure, i.e., connectivity. Answers to these questions shed novel insights on the structure of networks and how they react to perturbations.
Descriptive vs. mechanistic network models in plant development in the post-genomic era.

PubMed

Davila-Velderrain, J; Martinez-Garcia, J C; Alvarez-Buylla, E R

2015-01-01

Network modeling is now a widespread practice in systems biology, as well as in integrative genomics, and it constitutes a rich and diverse scientific research field. A conceptually clear understanding of the reasoning behind the main existing modeling approaches, and their associated technical terminologies, is required to avoid confusions and accelerate the transition towards an undeniable necessary more quantitative, multidisciplinary approach to biology. Herein, we focus on two main network-based modeling approaches that are commonly used depending on the information available and the intended goals: inference-based methods and system dynamics approaches. As far as data-based network inference methods are concerned, they enable the discovery of potential functional influences among molecular components. On the other hand, experimentally grounded network dynamical models have been shown to be perfectly suited for the mechanistic study of developmental processes. How do these two perspectives relate to each other? In this chapter, we describe and compare both approaches and then apply them to a given specific developmental module. Along with the step-by-step practical implementation of each approach, we also focus on discussing their respective goals, utility, assumptions, and associated limitations. We use the gene regulatory network (GRN) involved in Arabidopsis thaliana Root Stem Cell Niche patterning as our illustrative example. We show that descriptive models based on functional genomics data can provide important background information consistent with experimentally supported functional relationships integrated in mechanistic GRN models. The rationale of analysis and modeling can be applied to any other well-characterized functional developmental module in multicellular organisms, like plants and animals.
Wisdom of crowds for robust gene network inference

PubMed Central

Marbach, Daniel; Costello, James C.; Küffner, Robert; Vega, Nicci; Prill, Robert J.; Camacho, Diogo M.; Allison, Kyle R.; Kellis, Manolis; Collins, James J.; Stolovitzky, Gustavo

2012-01-01

Reconstructing gene regulatory networks from high-throughput data is a long-standing problem. Through the DREAM project (Dialogue on Reverse Engineering Assessment and Methods), we performed a comprehensive blind assessment of over thirty network inference methods on Escherichia coli, Staphylococcus aureus, Saccharomyces cerevisiae, and in silico microarray data. We characterize performance, data requirements, and inherent biases of different inference approaches offering guidelines for both algorithm application and development. We observe that no single inference method performs optimally across all datasets. In contrast, integration of predictions from multiple inference methods shows robust and high performance across diverse datasets. Thereby, we construct high-confidence networks for E. coli and S. aureus, each comprising ~1700 transcriptional interactions at an estimated precision of 50%. We experimentally test 53 novel interactions in E. coli, of which 23 were supported (43%). Our results establish community-based methods as a powerful and robust tool for the inference of transcriptional gene regulatory networks. PMID:22796662
Reconstructing blood stem cell regulatory network models from single-cell molecular profiles

PubMed Central

Hamey, Fiona K.; Nestorowa, Sonia; Kinston, Sarah J.; Kent, David G.; Wilson, Nicola K.

2017-01-01

Adult blood contains a mixture of mature cell types, each with specialized functions. Single hematopoietic stem cells (HSCs) have been functionally shown to generate all mature cell types for the lifetime of the organism. Differentiation of HSCs toward alternative lineages must be balanced at the population level by the fate decisions made by individual cells. Transcription factors play a key role in regulating these decisions and operate within organized regulatory programs that can be modeled as transcriptional regulatory networks. As dysregulation of single HSC fate decisions is linked to fatal malignancies such as leukemia, it is important to understand how these decisions are controlled on a cell-by-cell basis. Here we developed and applied a network inference method, exploiting the ability to infer dynamic information from single-cell snapshot expression data based on expression profiles of 48 genes in 2,167 blood stem and progenitor cells. This approach allowed us to infer transcriptional regulatory network models that recapitulated differentiation of HSCs into progenitor cell types, focusing on trajectories toward megakaryocyte–erythrocyte progenitors and lymphoid-primed multipotent progenitors. By comparing these two models, we identified and subsequently experimentally validated a difference in the regulation of nuclear factor, erythroid 2 (Nfe2) and core-binding factor, runt domain, alpha subunit 2, translocated to, 3 homolog (Cbfa2t3h) by the transcription factor Gata2. Our approach confirms known aspects of hematopoiesis, provides hypotheses about regulation of HSC differentiation, and is widely applicable to other hierarchical biological systems to uncover regulatory relationships. PMID:28584094
Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens

PubMed Central

Chasman, Deborah; Walters, Kevin B.; Lopes, Tiago J. S.; Eisfeld, Amie J.; Kawaoka, Yoshihiro; Roy, Sushmita

2016-01-01

Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection. PMID:27403523
MicroRNA-Target Network Inference and Local Network Enrichment Analysis Identify Two microRNA Clusters with Distinct Functions in Head and Neck Squamous Cell Carcinoma

PubMed Central

Sass, Steffen; Pitea, Adriana; Unger, Kristian; Hess, Julia; Mueller, Nikola S.; Theis, Fabian J.

2015-01-01

MicroRNAs represent ~22 nt long endogenous small RNA molecules that have been experimentally shown to regulate gene expression post-transcriptionally. One main interest in miRNA research is the investigation of their functional roles, which can typically be accomplished by identification of mi-/mRNA interactions and functional annotation of target gene sets. We here present a novel method “miRlastic”, which infers miRNA-target interactions using transcriptomic data as well as prior knowledge and performs functional annotation of target genes by exploiting the local structure of the inferred network. For the network inference, we applied linear regression modeling with elastic net regularization on matched microRNA and messenger RNA expression profiling data to perform feature selection on prior knowledge from sequence-based target prediction resources. The novelty of miRlastic inference originates in predicting data-driven intra-transcriptome regulatory relationships through feature selection. With synthetic data, we showed that miRlastic outperformed commonly used methods and was suitable even for low sample sizes. To gain insight into the functional role of miRNAs and to determine joint functional properties of miRNA clusters, we introduced a local enrichment analysis procedure. The principle of this procedure lies in identifying regions of high functional similarity by evaluating the shortest paths between genes in the network. We can finally assign functional roles to the miRNAs by taking their regulatory relationships into account. We thoroughly evaluated miRlastic on a cohort of head and neck cancer (HNSCC) patients provided by The Cancer Genome Atlas. We inferred an mi-/mRNA regulatory network for human papilloma virus (HPV)-associated miRNAs in HNSCC. The resulting network best enriched for experimentally validated miRNA-target interaction, when compared to common methods. Finally, the local enrichment step identified two functional clusters of miRNAs that were predicted to mediate HPV-associated dysregulation in HNSCC. Our novel approach was able to characterize distinct pathway regulations from matched miRNA and mRNA data. An R package of miRlastic was made available through: http://icb.helmholtz-muenchen.de/mirlastic. PMID:26694379
MicroRNA-Target Network Inference and Local Network Enrichment Analysis Identify Two microRNA Clusters with Distinct Functions in Head and Neck Squamous Cell Carcinoma.

PubMed

Sass, Steffen; Pitea, Adriana; Unger, Kristian; Hess, Julia; Mueller, Nikola S; Theis, Fabian J

2015-12-18

MicroRNAs represent ~22 nt long endogenous small RNA molecules that have been experimentally shown to regulate gene expression post-transcriptionally. One main interest in miRNA research is the investigation of their functional roles, which can typically be accomplished by identification of mi-/mRNA interactions and functional annotation of target gene sets. We here present a novel method "miRlastic", which infers miRNA-target interactions using transcriptomic data as well as prior knowledge and performs functional annotation of target genes by exploiting the local structure of the inferred network. For the network inference, we applied linear regression modeling with elastic net regularization on matched microRNA and messenger RNA expression profiling data to perform feature selection on prior knowledge from sequence-based target prediction resources. The novelty of miRlastic inference originates in predicting data-driven intra-transcriptome regulatory relationships through feature selection. With synthetic data, we showed that miRlastic outperformed commonly used methods and was suitable even for low sample sizes. To gain insight into the functional role of miRNAs and to determine joint functional properties of miRNA clusters, we introduced a local enrichment analysis procedure. The principle of this procedure lies in identifying regions of high functional similarity by evaluating the shortest paths between genes in the network. We can finally assign functional roles to the miRNAs by taking their regulatory relationships into account. We thoroughly evaluated miRlastic on a cohort of head and neck cancer (HNSCC) patients provided by The Cancer Genome Atlas. We inferred an mi-/mRNA regulatory network for human papilloma virus (HPV)-associated miRNAs in HNSCC. The resulting network best enriched for experimentally validated miRNA-target interaction, when compared to common methods. Finally, the local enrichment step identified two functional clusters of miRNAs that were predicted to mediate HPV-associated dysregulation in HNSCC. Our novel approach was able to characterize distinct pathway regulations from matched miRNA and mRNA data. An R package of miRlastic was made available through: http://icb.helmholtz-muenchen.de/mirlastic.
On the Inference of Functional Circadian Networks Using Granger Causality

PubMed Central

Pourzanjani, Arya; Herzog, Erik D.; Petzold, Linda R.

2015-01-01

Being able to infer one way direct connections in an oscillatory network such as the suprachiastmatic nucleus (SCN) of the mammalian brain using time series data is difficult but crucial to understanding network dynamics. Although techniques have been developed for inferring networks from time series data, there have been no attempts to adapt these techniques to infer directional connections in oscillatory time series, while accurately distinguishing between direct and indirect connections. In this paper an adaptation of Granger Causality is proposed that allows for inference of circadian networks and oscillatory networks in general called Adaptive Frequency Granger Causality (AFGC). Additionally, an extension of this method is proposed to infer networks with large numbers of cells called LASSO AFGC. The method was validated using simulated data from several different networks. For the smaller networks the method was able to identify all one way direct connections without identifying connections that were not present. For larger networks of up to twenty cells the method shows excellent performance in identifying true and false connections; this is quantified by an area-under-the-curve (AUC) 96.88%. We note that this method like other Granger Causality-based methods, is based on the detection of high frequency signals propagating between cell traces. Thus it requires a relatively high sampling rate and a network that can propagate high frequency signals. PMID:26413748
Inference of a Transcriptional Network Involved in Chemical Inhibition of Estrogen Synthesis in Fathead Minnow

EPA Science Inventory

A variety of chemicals in the environment have the potential to inhibit aromatase, an enzyme critical to estrogen synthesis. We examined the responses of female fathead minnows (Pimephales promelas) to a model aromatase inhibitor, fadrozole, using transcriptional network inferen...
A Systems Biology Approach to the Coordination of Defensive and Offensive Molecular Mechanisms in the Innate and Adaptive Host–Pathogen Interaction Networks

PubMed Central

Wu, Chia-Chou; Chen, Bor-Sen

2016-01-01

Infected zebrafish coordinates defensive and offensive molecular mechanisms in response to Candida albicans infections, and invasive C. albicans coordinates corresponding molecular mechanisms to interact with the host. However, knowledge of the ensuing infection-activated signaling networks in both host and pathogen and their interspecific crosstalk during the innate and adaptive phases of the infection processes remains incomplete. In the present study, dynamic network modeling, protein interaction databases, and dual transcriptome data from zebrafish and C. albicans during infection were used to infer infection-activated host–pathogen dynamic interaction networks. The consideration of host–pathogen dynamic interaction systems as innate and adaptive loops and subsequent comparisons of inferred innate and adaptive networks indicated previously unrecognized crosstalk between known pathways and suggested roles of immunological memory in the coordination of host defensive and offensive molecular mechanisms to achieve specific and powerful defense against pathogens. Moreover, pathogens enhance intraspecific crosstalk and abrogate host apoptosis to accommodate enhanced host defense mechanisms during the adaptive phase. Accordingly, links between physiological phenomena and changes in the coordination of defensive and offensive molecular mechanisms highlight the importance of host–pathogen molecular interaction networks, and consequent inferences of the host–pathogen relationship could be translated into biomedical applications. PMID:26881892
A Systems Biology Approach to the Coordination of Defensive and Offensive Molecular Mechanisms in the Innate and Adaptive Host-Pathogen Interaction Networks.

PubMed

Wu, Chia-Chou; Chen, Bor-Sen

2016-01-01

Infected zebrafish coordinates defensive and offensive molecular mechanisms in response to Candida albicans infections, and invasive C. albicans coordinates corresponding molecular mechanisms to interact with the host. However, knowledge of the ensuing infection-activated signaling networks in both host and pathogen and their interspecific crosstalk during the innate and adaptive phases of the infection processes remains incomplete. In the present study, dynamic network modeling, protein interaction databases, and dual transcriptome data from zebrafish and C. albicans during infection were used to infer infection-activated host-pathogen dynamic interaction networks. The consideration of host-pathogen dynamic interaction systems as innate and adaptive loops and subsequent comparisons of inferred innate and adaptive networks indicated previously unrecognized crosstalk between known pathways and suggested roles of immunological memory in the coordination of host defensive and offensive molecular mechanisms to achieve specific and powerful defense against pathogens. Moreover, pathogens enhance intraspecific crosstalk and abrogate host apoptosis to accommodate enhanced host defense mechanisms during the adaptive phase. Accordingly, links between physiological phenomena and changes in the coordination of defensive and offensive molecular mechanisms highlight the importance of host-pathogen molecular interaction networks, and consequent inferences of the host-pathogen relationship could be translated into biomedical applications.
Discovering novel phenotypes with automatically inferred dynamic models: a partial melanocyte conversion in Xenopus

NASA Astrophysics Data System (ADS)

Lobo, Daniel; Lobikin, Maria; Levin, Michael

2017-01-01

Progress in regenerative medicine requires reverse-engineering cellular control networks to infer perturbations with desired systems-level outcomes. Such dynamic models allow phenotypic predictions for novel perturbations to be rapidly assessed in silico. Here, we analyzed a Xenopus model of conversion of melanocytes to a metastatic-like phenotype only previously observed in an all-or-none manner. Prior in vivo genetic and pharmacological experiments showed that individual animals either fully convert or remain normal, at some characteristic frequency after a given perturbation. We developed a Machine Learning method which inferred a model explaining this complex, stochastic all-or-none dataset. We then used this model to ask how a new phenotype could be generated: animals in which only some of the melanocytes converted. Systematically performing in silico perturbations, the model predicted that a combination of altanserin (5HTR2 inhibitor), reserpine (VMAT inhibitor), and VP16-XlCreb1 (constitutively active CREB) would break the all-or-none concordance. Remarkably, applying the predicted combination of three reagents in vivo revealed precisely the expected novel outcome, resulting in partial conversion of melanocytes within individuals. This work demonstrates the capability of automated analysis of dynamic models of signaling networks to discover novel phenotypes and predictively identify specific manipulations that can reach them.
Mixture models with entropy regularization for community detection in networks

NASA Astrophysics Data System (ADS)

Chang, Zhenhai; Yin, Xianjun; Jia, Caiyan; Wang, Xiaoyang

2018-04-01

Community detection is a key exploratory tool in network analysis and has received much attention in recent years. NMM (Newman's mixture model) is one of the best models for exploring a range of network structures including community structure, bipartite and core-periphery structures, etc. However, NMM needs to know the number of communities in advance. Therefore, in this study, we have proposed an entropy regularized mixture model (called EMM), which is capable of inferring the number of communities and identifying network structure contained in a network, simultaneously. In the model, by minimizing the entropy of mixing coefficients of NMM using EM (expectation-maximization) solution, the small clusters contained little information can be discarded step by step. The empirical study on both synthetic networks and real networks has shown that the proposed model EMM is superior to the state-of-the-art methods.
Inferring gene regression networks with model trees

PubMed Central

2010-01-01

Background Novel strategies are required in order to handle the huge amount of data produced by microarray technologies. To infer gene regulatory networks, the first step is to find direct regulatory relationships between genes building the so-called gene co-expression networks. They are typically generated using correlation statistics as pairwise similarity measures. Correlation-based methods are very useful in order to determine whether two genes have a strong global similarity but do not detect local similarities. Results We propose model trees as a method to identify gene interaction networks. While correlation-based methods analyze each pair of genes, in our approach we generate a single regression tree for each gene from the remaining genes. Finally, a graph from all the relationships among output and input genes is built taking into account whether the pair of genes is statistically significant. For this reason we apply a statistical procedure to control the false discovery rate. The performance of our approach, named REGNET, is experimentally tested on two well-known data sets: Saccharomyces Cerevisiae and E.coli data set. First, the biological coherence of the results are tested. Second the E.coli transcriptional network (in the Regulon database) is used as control to compare the results to that of a correlation-based method. This experiment shows that REGNET performs more accurately at detecting true gene associations than the Pearson and Spearman zeroth and first-order correlation-based methods. Conclusions REGNET generates gene association networks from gene expression data, and differs from correlation-based methods in that the relationship between one gene and others is calculated simultaneously. Model trees are very useful techniques to estimate the numerical values for the target genes by linear regression functions. They are very often more precise than linear regression models because they can add just different linear regressions to separate areas of the search space favoring to infer localized similarities over a more global similarity. Furthermore, experimental results show the good performance of REGNET. PMID:20950452
Efficient probabilistic inference in generic neural networks trained with non-probabilistic feedback.

PubMed

Orhan, A Emin; Ma, Wei Ji

2017-07-26

Animals perform near-optimal probabilistic inference in a wide range of psychophysical tasks. Probabilistic inference requires trial-to-trial representation of the uncertainties associated with task variables and subsequent use of this representation. Previous work has implemented such computations using neural networks with hand-crafted and task-dependent operations. We show that generic neural networks trained with a simple error-based learning rule perform near-optimal probabilistic inference in nine common psychophysical tasks. In a probabilistic categorization task, error-based learning in a generic network simultaneously explains a monkey's learning curve and the evolution of qualitative aspects of its choice behavior. In all tasks, the number of neurons required for a given level of performance grows sublinearly with the input population size, a substantial improvement on previous implementations of probabilistic inference. The trained networks develop a novel sparsity-based probabilistic population code. Our results suggest that probabilistic inference emerges naturally in generic neural networks trained with error-based learning rules.Behavioural tasks often require probability distributions to be inferred about task specific variables. Here, the authors demonstrate that generic neural networks can be trained using a simple error-based learning rule to perform such probabilistic computations efficiently without any need for task specific operations.
Network diffusion accurately models the relationship between structural and functional brain connectivity networks

PubMed Central

Abdelnour, Farras; Voss, Henning U.; Raj, Ashish

2014-01-01

The relationship between anatomic connectivity of large-scale brain networks and their functional connectivity is of immense importance and an area of active research. Previous attempts have required complex simulations which model the dynamics of each cortical region, and explore the coupling between regions as derived by anatomic connections. While much insight is gained from these non-linear simulations, they can be computationally taxing tools for predicting functional from anatomic connectivities. Little attention has been paid to linear models. Here we show that a properly designed linear model appears to be superior to previous non-linear approaches in capturing the brain’s long-range second order correlation structure that governs the relationship between anatomic and functional connectivities. We derive a linear network of brain dynamics based on graph diffusion, whereby the diffusing quantity undergoes a random walk on a graph. We test our model using subjects who underwent diffusion MRI and resting state fMRI. The network diffusion model applied to the structural networks largely predicts the correlation structures derived from their fMRI data, to a greater extent than other approaches. The utility of the proposed approach is that it can routinely be used to infer functional correlation from anatomic connectivity. And since it is linear, anatomic connectivity can also be inferred from functional data. The success of our model confirms the linearity of ensemble average signals in the brain, and implies that their long-range correlation structure may percolate within the brain via purely mechanistic processes enacted on its structural connectivity pathways. PMID:24384152
Probability, statistics, and computational science.

PubMed

Beerenwinkel, Niko; Siebourg, Juliane

2012-01-01

In this chapter, we review basic concepts from probability theory and computational statistics that are fundamental to evolutionary genomics. We provide a very basic introduction to statistical modeling and discuss general principles, including maximum likelihood and Bayesian inference. Markov chains, hidden Markov models, and Bayesian network models are introduced in more detail as they occur frequently and in many variations in genomics applications. In particular, we discuss efficient inference algorithms and methods for learning these models from partially observed data. Several simple examples are given throughout the text, some of which point to models that are discussed in more detail in subsequent chapters.
Mass Conservation and Inference of Metabolic Networks from High-Throughput Mass Spectrometry Data

PubMed Central

Bandaru, Pradeep; Bansal, Mukesh

2011-01-01

Abstract We present a step towards the metabolome-wide computational inference of cellular metabolic reaction networks from metabolic profiling data, such as mass spectrometry. The reconstruction is based on identification of irreducible statistical interactions among the metabolite activities using the ARACNE reverse-engineering algorithm and on constraining possible metabolic transformations to satisfy the conservation of mass. The resulting algorithms are validated on synthetic data from an abridged computational model of Escherichia coli metabolism. Precision rates upwards of 50% are routinely observed for identification of full metabolic reactions, and recalls upwards of 20% are also seen. PMID:21314454
An argument for mechanism-based statistical inference in cancer

PubMed Central

Ochs, Michael; Price, Nathan D.; Tomasetti, Cristian; Younes, Laurent

2015-01-01

Cancer is perhaps the prototypical systems disease, and as such has been the focus of extensive study in quantitative systems biology. However, translating these programs into personalized clinical care remains elusive and incomplete. In this perspective, we argue that realizing this agenda—in particular, predicting disease phenotypes, progression and treatment response for individuals—requires going well beyond standard computational and bioinformatics tools and algorithms. It entails designing global mathematical models over network-scale configurations of genomic states and molecular concentrations, and learning the model parameters from limited available samples of high-dimensional and integrative omics data. As such, any plausible design should accommodate: biological mechanism, necessary for both feasible learning and interpretable decision making; stochasticity, to deal with uncertainty and observed variation at many scales; and a capacity for statistical inference at the patient level. This program, which requires a close, sustained collaboration between mathematicians and biologists, is illustrated in several contexts, including learning bio-markers, metabolism, cell signaling, network inference and tumorigenesis. PMID:25381197
U.S. stock market interaction network as learned by the Boltzmann machine

DOE PAGES

Borysov, Stanislav S.; Roudi, Yasser; Balatsky, Alexander V.

2015-12-07

Here, we study historical dynamics of joint equilibrium distribution of stock returns in the U.S. stock market using the Boltzmann distribution model being parametrized by external fields and pairwise couplings. Within Boltzmann learning framework for statistical inference, we analyze historical behavior of the parameters inferred using exact and approximate learning algorithms. Since the model and inference methods require use of binary variables, effect of this mapping of continuous returns to the discrete domain is studied. The presented results show that binarization preserves the correlation structure of the market. Properties of distributions of external fields and couplings as well as themore » market interaction network and industry sector clustering structure are studied for different historical dates and moving window sizes. We demonstrate that the observed positive heavy tail in distribution of couplings is related to the sparse clustering structure of the market. We also show that discrepancies between the model’s parameters might be used as a precursor of financial instabilities.« less

Using soft computing techniques to predict corrected air permeability using Thomeer parameters, air porosity and grain density

NASA Astrophysics Data System (ADS)

Nooruddin, Hasan A.; Anifowose, Fatai; Abdulraheem, Abdulazeez

2014-03-01

Soft computing techniques are recently becoming very popular in the oil industry. A number of computational intelligence-based predictive methods have been widely applied in the industry with high prediction capabilities. Some of the popular methods include feed-forward neural networks, radial basis function network, generalized regression neural network, functional networks, support vector regression and adaptive network fuzzy inference system. A comparative study among most popular soft computing techniques is presented using a large dataset published in literature describing multimodal pore systems in the Arab D formation. The inputs to the models are air porosity, grain density, and Thomeer parameters obtained using mercury injection capillary pressure profiles. Corrected air permeability is the target variable. Applying developed permeability models in recent reservoir characterization workflow ensures consistency between micro and macro scale information represented mainly by Thomeer parameters and absolute permeability. The dataset was divided into two parts with 80% of data used for training and 20% for testing. The target permeability variable was transformed to the logarithmic scale as a pre-processing step and to show better correlations with the input variables. Statistical and graphical analysis of the results including permeability cross-plots and detailed error measures were created. In general, the comparative study showed very close results among the developed models. The feed-forward neural network permeability model showed the lowest average relative error, average absolute relative error, standard deviations of error and root means squares making it the best model for such problems. Adaptive network fuzzy inference system also showed very good results.
Inference of Gene Regulatory Networks Incorporating Multi-Source Biological Knowledge via a State Space Model with L1 Regularization

PubMed Central

Hasegawa, Takanori; Yamaguchi, Rui; Nagasaki, Masao; Miyano, Satoru; Imoto, Seiya

2014-01-01

Comprehensive understanding of gene regulatory networks (GRNs) is a major challenge in the field of systems biology. Currently, there are two main approaches in GRN analysis using time-course observation data, namely an ordinary differential equation (ODE)-based approach and a statistical model-based approach. The ODE-based approach can generate complex dynamics of GRNs according to biologically validated nonlinear models. However, it cannot be applied to ten or more genes to simultaneously estimate system dynamics and regulatory relationships due to the computational difficulties. The statistical model-based approach uses highly abstract models to simply describe biological systems and to infer relationships among several hundreds of genes from the data. However, the high abstraction generates false regulations that are not permitted biologically. Thus, when dealing with several tens of genes of which the relationships are partially known, a method that can infer regulatory relationships based on a model with low abstraction and that can emulate the dynamics of ODE-based models while incorporating prior knowledge is urgently required. To accomplish this, we propose a method for inference of GRNs using a state space representation of a vector auto-regressive (VAR) model with L1 regularization. This method can estimate the dynamic behavior of genes based on linear time-series modeling constructed from an ODE-based model and can infer the regulatory structure among several tens of genes maximizing prediction ability for the observational data. Furthermore, the method is capable of incorporating various types of existing biological knowledge, e.g., drug kinetics and literature-recorded pathways. The effectiveness of the proposed method is shown through a comparison of simulation studies with several previous methods. For an application example, we evaluated mRNA expression profiles over time upon corticosteroid stimulation in rats, thus incorporating corticosteroid kinetics/dynamics, literature-recorded pathways and transcription factor (TF) information. PMID:25162401
Compartmentalized gene regulatory network of the pathogenic fungus Fusarium graminearum

USDA-ARS?s Scientific Manuscript database

Head blight caused by Fusarium graminearum (Fg) is a major limiting factor of wheat production with both yield loss and mycotoxin contamination. Here we report a model for global Fg gene regulatory networks (GRNs) inferred from a large collection of transcriptomic data using a machine-learning appro...
Network inference from multimodal data: A review of approaches from infectious disease transmission.

PubMed

Ray, Bisakha; Ghedin, Elodie; Chunara, Rumi

2016-12-01

Networks inference problems are commonly found in multiple biomedical subfields such as genomics, metagenomics, neuroscience, and epidemiology. Networks are useful for representing a wide range of complex interactions ranging from those between molecular biomarkers, neurons, and microbial communities, to those found in human or animal populations. Recent technological advances have resulted in an increasing amount of healthcare data in multiple modalities, increasing the preponderance of network inference problems. Multi-domain data can now be used to improve the robustness and reliability of recovered networks from unimodal data. For infectious diseases in particular, there is a body of knowledge that has been focused on combining multiple pieces of linked information. Combining or analyzing disparate modalities in concert has demonstrated greater insight into disease transmission than could be obtained from any single modality in isolation. This has been particularly helpful in understanding incidence and transmission at early stages of infections that have pandemic potential. Novel pieces of linked information in the form of spatial, temporal, and other covariates including high-throughput sequence data, clinical visits, social network information, pharmaceutical prescriptions, and clinical symptoms (reported as free-text data) also encourage further investigation of these methods. The purpose of this review is to provide an in-depth analysis of multimodal infectious disease transmission network inference methods with a specific focus on Bayesian inference. We focus on analytical Bayesian inference-based methods as this enables recovering multiple parameters simultaneously, for example, not just the disease transmission network, but also parameters of epidemic dynamics. Our review studies their assumptions, key inference parameters and limitations, and ultimately provides insights about improving future network inference methods in multiple applications. Copyright Â© 2016 Elsevier Inc. All rights reserved.
Bayesian Networks Improve Causal Environmental Assessments for Evidence-Based Policy.

PubMed

Carriger, John F; Barron, Mace G; Newman, Michael C

2016-12-20

Rule-based weight of evidence approaches to ecological risk assessment may not account for uncertainties and generally lack probabilistic integration of lines of evidence. Bayesian networks allow causal inferences to be made from evidence by including causal knowledge about the problem, using this knowledge with probabilistic calculus to combine multiple lines of evidence, and minimizing biases in predicting or diagnosing causal relationships. Too often, sources of uncertainty in conventional weight of evidence approaches are ignored that can be accounted for with Bayesian networks. Specifying and propagating uncertainties improve the ability of models to incorporate strength of the evidence in the risk management phase of an assessment. Probabilistic inference from a Bayesian network allows evaluation of changes in uncertainty for variables from the evidence. The network structure and probabilistic framework of a Bayesian approach provide advantages over qualitative approaches in weight of evidence for capturing the impacts of multiple sources of quantifiable uncertainty on predictions of ecological risk. Bayesian networks can facilitate the development of evidence-based policy under conditions of uncertainty by incorporating analytical inaccuracies or the implications of imperfect information, structuring and communicating causal issues through qualitative directed graph formulations, and quantitatively comparing the causal power of multiple stressors on valued ecological resources. These aspects are demonstrated through hypothetical problem scenarios that explore some major benefits of using Bayesian networks for reasoning and making inferences in evidence-based policy.
Learning a Markov Logic network for supervised gene regulatory network inference

PubMed Central

2013-01-01

Background Gene regulatory network inference remains a challenging problem in systems biology despite the numerous approaches that have been proposed. When substantial knowledge on a gene regulatory network is already available, supervised network inference is appropriate. Such a method builds a binary classifier able to assign a class (Regulation/No regulation) to an ordered pair of genes. Once learnt, the pairwise classifier can be used to predict new regulations. In this work, we explore the framework of Markov Logic Networks (MLN) that combine features of probabilistic graphical models with the expressivity of first-order logic rules. Results We propose to learn a Markov Logic network, e.g. a set of weighted rules that conclude on the predicate “regulates”, starting from a known gene regulatory network involved in the switch proliferation/differentiation of keratinocyte cells, a set of experimental transcriptomic data and various descriptions of genes all encoded into first-order logic. As training data are unbalanced, we use asymmetric bagging to learn a set of MLNs. The prediction of a new regulation can then be obtained by averaging predictions of individual MLNs. As a side contribution, we propose three in silico tests to assess the performance of any pairwise classifier in various network inference tasks on real datasets. A first test consists of measuring the average performance on balanced edge prediction problem; a second one deals with the ability of the classifier, once enhanced by asymmetric bagging, to update a given network. Finally our main result concerns a third test that measures the ability of the method to predict regulations with a new set of genes. As expected, MLN, when provided with only numerical discretized gene expression data, does not perform as well as a pairwise SVM in terms of AUPR. However, when a more complete description of gene properties is provided by heterogeneous sources, MLN achieves the same performance as a black-box model such as a pairwise SVM while providing relevant insights on the predictions. Conclusions The numerical studies show that MLN achieves very good predictive performance while opening the door to some interpretability of the decisions. Besides the ability to suggest new regulations, such an approach allows to cross-validate experimental data with existing knowledge. PMID:24028533
Learning a Markov Logic network for supervised gene regulatory network inference.

PubMed

Brouard, Céline; Vrain, Christel; Dubois, Julie; Castel, David; Debily, Marie-Anne; d'Alché-Buc, Florence

2013-09-12

Gene regulatory network inference remains a challenging problem in systems biology despite the numerous approaches that have been proposed. When substantial knowledge on a gene regulatory network is already available, supervised network inference is appropriate. Such a method builds a binary classifier able to assign a class (Regulation/No regulation) to an ordered pair of genes. Once learnt, the pairwise classifier can be used to predict new regulations. In this work, we explore the framework of Markov Logic Networks (MLN) that combine features of probabilistic graphical models with the expressivity of first-order logic rules. We propose to learn a Markov Logic network, e.g. a set of weighted rules that conclude on the predicate "regulates", starting from a known gene regulatory network involved in the switch proliferation/differentiation of keratinocyte cells, a set of experimental transcriptomic data and various descriptions of genes all encoded into first-order logic. As training data are unbalanced, we use asymmetric bagging to learn a set of MLNs. The prediction of a new regulation can then be obtained by averaging predictions of individual MLNs. As a side contribution, we propose three in silico tests to assess the performance of any pairwise classifier in various network inference tasks on real datasets. A first test consists of measuring the average performance on balanced edge prediction problem; a second one deals with the ability of the classifier, once enhanced by asymmetric bagging, to update a given network. Finally our main result concerns a third test that measures the ability of the method to predict regulations with a new set of genes. As expected, MLN, when provided with only numerical discretized gene expression data, does not perform as well as a pairwise SVM in terms of AUPR. However, when a more complete description of gene properties is provided by heterogeneous sources, MLN achieves the same performance as a black-box model such as a pairwise SVM while providing relevant insights on the predictions. The numerical studies show that MLN achieves very good predictive performance while opening the door to some interpretability of the decisions. Besides the ability to suggest new regulations, such an approach allows to cross-validate experimental data with existing knowledge.
A Scalable Approach to Modeling Cascading Risk in the MDAP Network

DTIC Science & Technology

2014-04-30

our future work. References Asuncion, A., Welling, M., Smyth, P., & Teh , P. Y. ( 2009 ). On Smoothing and inference for Topic Models, Proceeding of...modeling can be measured using a factor called perplexity (Asuncion et al., 2009 ). Perplexity is a measure of model’s ability to infer the topics in...fåÑçêãÉÇ=`Ü~åÖÉ= = - 307 - Table 5. Funding Table for FY 2007 From PE_abc (From 2009 Document) Programs Cost ($ in millions) for FY 2007 Non-MDAP_a
Comprehensive heat transfer correlation for water/ethylene glycol-based graphene (nitrogen-doped graphene) nanofluids derived by artificial neural network (ANN) and adaptive neuro-fuzzy inference system (ANFIS)

NASA Astrophysics Data System (ADS)

Savari, Maryam; Moghaddam, Amin Hedayati; Amiri, Ahmad; Shanbedi, Mehdi; Ayub, Mohamad Nizam Bin

2017-10-01

Herein, artificial neural network and adaptive neuro-fuzzy inference system are employed for modeling the effects of important parameters on heat transfer and fluid flow characteristics of a car radiator and followed by comparing with those of the experimental results for testing data. To this end, two novel nanofluids (water/ethylene glycol-based graphene and nitrogen-doped graphene nanofluids) were experimentally synthesized. Then, Nusselt number was modeled with respect to the variation of inlet temperature, Reynolds number, Prandtl number and concentration, which were defined as the input (design) variables. To reach reliable results, we divided these data into train and test sections to accomplish modeling. Artificial networks were instructed by a major part of experimental data. The other part of primary data which had been considered for testing the appropriateness of the models was entered into artificial network models. Finally, predictad results were compared to the experimental data to evaluate validity. Confronted with high-level of validity confirmed that the proposed modeling procedure by BPNN with one hidden layer and five neurons is efficient and it can be expanded for all water/ethylene glycol-based carbon nanostructures nanofluids. Finally, we expanded our data collection from model and could present a fundamental correlation for calculating Nusselt number of the water/ethylene glycol-based nanofluids including graphene or nitrogen-doped graphene.
A comparative study of covariance selection models for the inference of gene regulatory networks.

PubMed

Stifanelli, Patrizia F; Creanza, Teresa M; Anglani, Roberto; Liuzzi, Vania C; Mukherjee, Sayan; Schena, Francesco P; Ancona, Nicola

2013-10-01

The inference, or 'reverse-engineering', of gene regulatory networks from expression data and the description of the complex dependency structures among genes are open issues in modern molecular biology. In this paper we compared three regularized methods of covariance selection for the inference of gene regulatory networks, developed to circumvent the problems raising when the number of observations n is smaller than the number of genes p. The examined approaches provided three alternative estimates of the inverse covariance matrix: (a) the 'PINV' method is based on the Moore-Penrose pseudoinverse, (b) the 'RCM' method performs correlation between regression residuals and (c) 'ℓ(2C)' method maximizes a properly regularized log-likelihood function. Our extensive simulation studies showed that ℓ(2C) outperformed the other two methods having the most predictive partial correlation estimates and the highest values of sensitivity to infer conditional dependencies between genes even when a few number of observations was available. The application of this method for inferring gene networks of the isoprenoid biosynthesis pathways in Arabidopsis thaliana allowed to enlighten a negative partial correlation coefficient between the two hubs in the two isoprenoid pathways and, more importantly, provided an evidence of cross-talk between genes in the plastidial and the cytosolic pathways. When applied to gene expression data relative to a signature of HRAS oncogene in human cell cultures, the method revealed 9 genes (p-value<0.0005) directly interacting with HRAS, sharing the same Ras-responsive binding site for the transcription factor RREB1. This result suggests that the transcriptional activation of these genes is mediated by a common transcription factor downstream of Ras signaling. Software implementing the methods in the form of Matlab scripts are available at: http://users.ba.cnr.it/issia/iesina18/CovSelModelsCodes.zip. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.
Inferring transcriptional gene regulation network of starch metabolism in Arabidopsis thaliana leaves using graphical Gaussian model

PubMed Central

2012-01-01

Background Starch serves as a temporal storage of carbohydrates in plant leaves during day/night cycles. To study transcriptional regulatory modules of this dynamic metabolic process, we conducted gene regulation network analysis based on small-sample inference of graphical Gaussian model (GGM). Results Time-series significant analysis was applied for Arabidopsis leaf transcriptome data to obtain a set of genes that are highly regulated under a diurnal cycle. A total of 1,480 diurnally regulated genes included 21 starch metabolic enzymes, 6 clock-associated genes, and 106 transcription factors (TF). A starch-clock-TF gene regulation network comprising 117 nodes and 266 edges was constructed by GGM from these 133 significant genes that are potentially related to the diurnal control of starch metabolism. From this network, we found that β-amylase 3 (b-amy3: At4g17090), which participates in starch degradation in chloroplast, is the most frequently connected gene (a hub gene). The robustness of gene-to-gene regulatory network was further analyzed by TF binding site prediction and by evaluating global co-expression of TFs and target starch metabolic enzymes. As a result, two TFs, indeterminate domain 5 (AtIDD5: At2g02070) and constans-like (COL: At2g21320), were identified as positive regulators of starch synthase 4 (SS4: At4g18240). The inference model of AtIDD5-dependent positive regulation of SS4 gene expression was experimentally supported by decreased SS4 mRNA accumulation in Atidd5 mutant plants during the light period of both short and long day conditions. COL was also shown to positively control SS4 mRNA accumulation. Furthermore, the knockout of AtIDD5 and COL led to deformation of chloroplast and its contained starch granules. This deformity also affected the number of starch granules per chloroplast, which increased significantly in both knockout mutant lines. Conclusions In this study, we utilized a systematic approach of microarray analysis to discover the transcriptional regulatory network of starch metabolism in Arabidopsis leaves. With this inference method, the starch regulatory network of Arabidopsis was found to be strongly associated with clock genes and TFs, of which AtIDD5 and COL were evidenced to control SS4 gene expression and starch granule formation in chloroplasts. PMID:22898356
Determining geophysical properties from well log data using artificial neural networks and fuzzy inference systems

NASA Astrophysics Data System (ADS)

Chang, Hsien-Cheng

Two novel synergistic systems consisting of artificial neural networks and fuzzy inference systems are developed to determine geophysical properties by using well log data. These systems are employed to improve the determination accuracy in carbonate rocks, which are generally more complex than siliciclastic rocks. One system, consisting of a single adaptive resonance theory (ART) neural network and three fuzzy inference systems (FISs), is used to determine the permeability category. The other system, which is composed of three ART neural networks and a single FIS, is employed to determine the lithofacies. The geophysical properties studied in this research, permeability category and lithofacies, are treated as categorical data. The permeability values are transformed into a "permeability category" to account for the effects of scale differences between core analyses and well logs, and heterogeneity in the carbonate rocks. The ART neural networks dynamically cluster the input data sets into different groups. The FIS is used to incorporate geologic experts' knowledge, which is usually in linguistic forms, into systems. These synergistic systems thus provide viable alternative solutions to overcome the effects of heterogeneity, the uncertainties of carbonate rock depositional environments, and the scarcity of well log data. The results obtained in this research show promising improvements over backpropagation neural networks. For the permeability category, the prediction accuracies are 68.4% and 62.8% for the multiple-single ART neural network-FIS and a single backpropagation neural network, respectively. For lithofacies, the prediction accuracies are 87.6%, 79%, and 62.8% for the single-multiple ART neural network-FIS, a single ART neural network, and a single backpropagation neural network, respectively. The sensitivity analysis results show that the multiple-single ART neural networks-FIS and a single ART neural network possess the same matching trends in determining lithofacies. This research shows that the adaptive resonance theory neural networks enable decision-makers to clearly distinguish the importance of different pieces of data which are useful in three-dimensional subsurface modeling. Geologic experts' knowledge can be easily applied and maintained by using the fuzzy inference systems.
Neural Dynamics as Sampling: A Model for Stochastic Computation in Recurrent Networks of Spiking Neurons

PubMed Central

Buesing, Lars; Bill, Johannes; Nessler, Bernhard; Maass, Wolfgang

2011-01-01

The organization of computations in networks of spiking neurons in the brain is still largely unknown, in particular in view of the inherently stochastic features of their firing activity and the experimentally observed trial-to-trial variability of neural systems in the brain. In principle there exists a powerful computational framework for stochastic computations, probabilistic inference by sampling, which can explain a large number of macroscopic experimental data in neuroscience and cognitive science. But it has turned out to be surprisingly difficult to create a link between these abstract models for stochastic computations and more detailed models of the dynamics of networks of spiking neurons. Here we create such a link and show that under some conditions the stochastic firing activity of networks of spiking neurons can be interpreted as probabilistic inference via Markov chain Monte Carlo (MCMC) sampling. Since common methods for MCMC sampling in distributed systems, such as Gibbs sampling, are inconsistent with the dynamics of spiking neurons, we introduce a different approach based on non-reversible Markov chains that is able to reflect inherent temporal processes of spiking neuronal activity through a suitable choice of random variables. We propose a neural network model and show by a rigorous theoretical analysis that its neural activity implements MCMC sampling of a given distribution, both for the case of discrete and continuous time. This provides a step towards closing the gap between abstract functional models of cortical computation and more detailed models of networks of spiking neurons. PMID:22096452
Do people reason rationally about causally related events? Markov violations, weak inferences, and failures of explaining away.

PubMed

Rottman, Benjamin M; Hastie, Reid

2016-06-01

Making judgments by relying on beliefs about the causal relationships between events is a fundamental capacity of everyday cognition. In the last decade, Causal Bayesian Networks have been proposed as a framework for modeling causal reasoning. Two experiments were conducted to provide comprehensive data sets with which to evaluate a variety of different types of judgments in comparison to the standard Bayesian networks calculations. Participants were introduced to a fictional system of three events and observed a set of learning trials that instantiated the multivariate distribution relating the three variables. We tested inferences on chains X1→Y→X2, common cause structures X1←Y→X2, and common effect structures X1→Y←X2, on binary and numerical variables, and with high and intermediate causal strengths. We tested transitive inferences, inferences when one variable is irrelevant because it is blocked by an intervening variable (Markov Assumption), inferences from two variables to a middle variable, and inferences about the presence of one cause when the alternative cause was known to have occurred (the normative "explaining away" pattern). Compared to the normative account, in general, when the judgments should change, they change in the normative direction. However, we also discuss a few persistent violations of the standard normative model. In addition, we evaluate the relative success of 12 theoretical explanations for these deviations. Copyright © 2016 Elsevier Inc. All rights reserved.
Using Neural Networks to Generate Inferential Roles for Natural Language

PubMed Central

Blouw, Peter; Eliasmith, Chris

2018-01-01

Neural networks have long been used to study linguistic phenomena spanning the domains of phonology, morphology, syntax, and semantics. Of these domains, semantics is somewhat unique in that there is little clarity concerning what a model needs to be able to do in order to provide an account of how the meanings of complex linguistic expressions, such as sentences, are understood. We argue that one thing such models need to be able to do is generate predictions about which further sentences are likely to follow from a given sentence; these define the sentence's “inferential role.” We then show that it is possible to train a tree-structured neural network model to generate very simple examples of such inferential roles using the recently released Stanford Natural Language Inference (SNLI) dataset. On an empirical front, we evaluate the performance of this model by reporting entailment prediction accuracies on a set of test sentences not present in the training data. We also report the results of a simple study that compares human plausibility ratings for both human-generated and model-generated entailments for a random selection of sentences in this test set. On a more theoretical front, we argue in favor of a revision to some common assumptions about semantics: understanding a linguistic expression is not only a matter of mapping it onto a representation that somehow constitutes its meaning; rather, understanding a linguistic expression is mainly a matter of being able to draw certain inferences. Inference should accordingly be at the core of any model of semantic cognition. PMID:29387031
Distinguishing between direct and indirect directional couplings in large oscillator networks: Partial or non-partial phase analyses?

NASA Astrophysics Data System (ADS)

Rings, Thorsten; Lehnertz, Klaus

2016-09-01

We investigate the relative merit of phase-based methods for inferring directional couplings in complex networks of weakly interacting dynamical systems from multivariate time-series data. We compare the evolution map approach and its partialized extension to each other with respect to their ability to correctly infer the network topology in the presence of indirect directional couplings for various simulated experimental situations using coupled model systems. In addition, we investigate whether the partialized approach allows for additional or complementary indications of directional interactions in evolving epileptic brain networks using intracranial electroencephalographic recordings from an epilepsy patient. For such networks, both direct and indirect directional couplings can be expected, given the brain's connection structure and effects that may arise from limitations inherent to the recording technique. Our findings indicate that particularly in larger networks (number of nodes ≫10 ), the partialized approach does not provide information about directional couplings extending the information gained with the evolution map approach.
Parameter inference in small world network disease models with approximate Bayesian Computational methods

NASA Astrophysics Data System (ADS)

Walker, David M.; Allingham, David; Lee, Heung Wing Joseph; Small, Michael

2010-02-01

Small world network models have been effective in capturing the variable behaviour of reported case data of the SARS coronavirus outbreak in Hong Kong during 2003. Simulations of these models have previously been realized using informed “guesses” of the proposed model parameters and tested for consistency with the reported data by surrogate analysis. In this paper we attempt to provide statistically rigorous parameter distributions using Approximate Bayesian Computation sampling methods. We find that such sampling schemes are a useful framework for fitting parameters of stochastic small world network models where simulation of the system is straightforward but expressing a likelihood is cumbersome.
Supervised dictionary learning for inferring concurrent brain networks.

PubMed

Zhao, Shijie; Han, Junwei; Lv, Jinglei; Jiang, Xi; Hu, Xintao; Zhao, Yu; Ge, Bao; Guo, Lei; Liu, Tianming

2015-10-01

Task-based fMRI (tfMRI) has been widely used to explore functional brain networks via predefined stimulus paradigm in the fMRI scan. Traditionally, the general linear model (GLM) has been a dominant approach to detect task-evoked networks. However, GLM focuses on task-evoked or event-evoked brain responses and possibly ignores the intrinsic brain functions. In comparison, dictionary learning and sparse coding methods have attracted much attention recently, and these methods have shown the promise of automatically and systematically decomposing fMRI signals into meaningful task-evoked and intrinsic concurrent networks. Nevertheless, two notable limitations of current data-driven dictionary learning method are that the prior knowledge of task paradigm is not sufficiently utilized and that the establishment of correspondences among dictionary atoms in different brains have been challenging. In this paper, we propose a novel supervised dictionary learning and sparse coding method for inferring functional networks from tfMRI data, which takes both of the advantages of model-driven method and data-driven method. The basic idea is to fix the task stimulus curves as predefined model-driven dictionary atoms and only optimize the other portion of data-driven dictionary atoms. Application of this novel methodology on the publicly available human connectome project (HCP) tfMRI datasets has achieved promising results.
Functional network inference of the suprachiasmatic nucleus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abel, John H.; Meeker, Kirsten; Granados-Fuentes, Daniel

2016-04-04

In the mammalian suprachiasmatic nucleus (SCN), noisy cellular oscillators communicate within a neuronal network to generate precise system-wide circadian rhythms. Although the intracellular genetic oscillator and intercellular biochemical coupling mechanisms have been examined previously, the network topology driving synchronization of the SCN has not been elucidated. This network has been particularly challenging to probe, due to its oscillatory components and slow coupling timescale. In this work, we investigated the SCN network at a single-cell resolution through a chemically induced desynchronization. We then inferred functional connections in the SCN by applying the maximal information coefficient statistic to bioluminescence reporter data frommore » individual neurons while they resynchronized their circadian cycling. Our results demonstrate that the functional network of circadian cells associated with resynchronization has small-world characteristics, with a node degree distribution that is exponential. We show that hubs of this small-world network are preferentially located in the central SCN, with sparsely connected shells surrounding these cores. Finally, we used two computational models of circadian neurons to validate our predictions of network structure.« less
Evaluating the Limits of Network Topology Inference Via Virtualized Network Emulation

DTIC Science & Technology

2015-06-01

76 xi Figure 5.33 Hop-plot of five best reduction methods. KDD most closely matches the Internet plot...respectively, located around the world. These monitors provide locations from which to perform network measurement experiments, primarily using the ping ...International Symposium on Modeling, Analysis and Simulation of Computer Telecommunication Systems. IEEE, 2001, pp. 346–353. 90 [21] C. Jin , Q. Chen, and S

Ensembles of Spiking Neurons with Noise Support Optimal Probabilistic Inference in a Dynamically Changing Environment

PubMed Central

Legenstein, Robert; Maass, Wolfgang

2014-01-01

It has recently been shown that networks of spiking neurons with noise can emulate simple forms of probabilistic inference through “neural sampling”, i.e., by treating spikes as samples from a probability distribution of network states that is encoded in the network. Deficiencies of the existing model are its reliance on single neurons for sampling from each random variable, and the resulting limitation in representing quickly varying probabilistic information. We show that both deficiencies can be overcome by moving to a biologically more realistic encoding of each salient random variable through the stochastic firing activity of an ensemble of neurons. The resulting model demonstrates that networks of spiking neurons with noise can easily track and carry out basic computational operations on rapidly varying probability distributions, such as the odds of getting rewarded for a specific behavior. We demonstrate the viability of this new approach towards neural coding and computation, which makes use of the inherent parallelism of generic neural circuits, by showing that this model can explain experimentally observed firing activity of cortical neurons for a variety of tasks that require rapid temporal integration of sensory information. PMID:25340749
Combinatorial influence of environmental parameters on transcription factor activity

PubMed Central

Knijnenburg, T.A.; Wessels, L.F.A.; Reinders, M.J.T.

2008-01-01

Motivation: Cells receive a wide variety of environmental signals, which are often processed combinatorially to generate specific genetic responses. Changes in transcript levels, as observed across different environmental conditions, can, to a large extent, be attributed to changes in the activity of transcription factors (TFs). However, in unraveling these transcription regulation networks, the actual environmental signals are often not incorporated into the model, simply because they have not been measured. The unquantified heterogeneity of the environmental parameters across microarray experiments frustrates regulatory network inference. Results: We propose an inference algorithm that models the influence of environmental parameters on gene expression. The approach is based on a yeast microarray compendium of chemostat steady-state experiments. Chemostat cultivation enables the accurate control and measurement of many of the key cultivation parameters, such as nutrient concentrations, growth rate and temperature. The observed transcript levels are explained by inferring the activity of TFs in response to combinations of cultivation parameters. The interplay between activated enhancers and repressors that bind a gene promoter determine the possible up- or downregulation of the gene. The model is translated into a linear integer optimization problem. The resulting regulatory network identifies the combinatorial effects of environmental parameters on TF activity and gene expression. Availability: The Matlab code is available from the authors upon request. Contact: t.a.knijnenburg@tudelft.nl Supplementary information: Supplementary data are available at Bioinformatics online. PMID:18586711
Network inference reveals novel connections in pathways regulating growth and defense in the yeast salt response.

PubMed

MacGilvray, Matthew E; Shishkova, Evgenia; Chasman, Deborah; Place, Michael; Gitter, Anthony; Coon, Joshua J; Gasch, Audrey P

2018-05-01

Cells respond to stressful conditions by coordinating a complex, multi-faceted response that spans many levels of physiology. Much of the response is coordinated by changes in protein phosphorylation. Although the regulators of transcriptome changes during stress are well characterized in Saccharomyces cerevisiae, the upstream regulatory network controlling protein phosphorylation is less well dissected. Here, we developed a computational approach to infer the signaling network that regulates phosphorylation changes in response to salt stress. We developed an approach to link predicted regulators to groups of likely co-regulated phospho-peptides responding to stress, thereby creating new edges in a background protein interaction network. We then use integer linear programming (ILP) to integrate wild type and mutant phospho-proteomic data and predict the network controlling stress-activated phospho-proteomic changes. The network we inferred predicted new regulatory connections between stress-activated and growth-regulating pathways and suggested mechanisms coordinating metabolism, cell-cycle progression, and growth during stress. We confirmed several network predictions with co-immunoprecipitations coupled with mass-spectrometry protein identification and mutant phospho-proteomic analysis. Results show that the cAMP-phosphodiesterase Pde2 physically interacts with many stress-regulated transcription factors targeted by PKA, and that reduced phosphorylation of those factors during stress requires the Rck2 kinase that we show physically interacts with Pde2. Together, our work shows how a high-quality computational network model can facilitate discovery of new pathway interactions during osmotic stress.
Mineral and Geochemical Classification From Spectroscopy/Diffraction Through Neural Networks

NASA Astrophysics Data System (ADS)

Ferralis, N.; Grossman, J.; Summons, R. E.

2017-12-01

Spectroscopy and diffraction techniques are essential for understanding structural, chemical and functional properties of geological materials for Earth and Planetary Sciences. Beyond data collection, quantitative insight relies on experimentally assembled, or computationally derived spectra. Inference on the geochemical or geophysical properties (such as crystallographic order, chemical functionality, elemental composition, etc.) of a particular geological material (mineral, organic matter, etc.) is based on fitting unknown spectra and comparing the fit with consolidated databases. The complexity of fitting highly convoluted spectra, often limits the ability to infer geochemical characteristics, and limits the throughput for extensive datasets. With the emergence of heuristic approaches to pattern recognitions though machine learning, in this work we investigate the possibility and potential of using supervised neural networks trained on available public spectroscopic database to directly infer geochemical parameters from unknown spectra. Using Raman, infrared spectroscopy and powder x-ray diffraction from the publicly available RRUFF database, we train neural network models to classify mineral and organic compounds (pure or mixtures) based on crystallographic structure from diffraction, chemical functionality, elemental composition and bonding from spectroscopy. As expected, the accuracy of the inference is strongly dependent on the quality and extent of the training data. We will identify a series of requirements and guidelines for the training dataset needed to achieve consistent high accuracy inference, along with methods to compensate for limited of data.
A descriptive model of resting-state networks using Markov chains.

PubMed

Xie, H; Pal, R; Mitra, S

2016-08-01

Resting-state functional connectivity (RSFC) studies considering pairwise linear correlations have attracted great interests while the underlying functional network structure still remains poorly understood. To further our understanding of RSFC, this paper presents an analysis of the resting-state networks (RSNs) based on the steady-state distributions and provides a novel angle to investigate the RSFC of multiple functional nodes. This paper evaluates the consistency of two networks based on the Hellinger distance between the steady-state distributions of the inferred Markov chain models. The results show that generated steady-state distributions of default mode network have higher consistency across subjects than random nodes from various RSNs.
Data mining in forecasting PVT correlations of crude oil systems based on Type1 fuzzy logic inference systems

NASA Astrophysics Data System (ADS)

El-Sebakhy, Emad A.

2009-09-01

Pressure-volume-temperature properties are very important in the reservoir engineering computations. There are many empirical approaches for predicting various PVT properties based on empirical correlations and statistical regression models. Last decade, researchers utilized neural networks to develop more accurate PVT correlations. These achievements of neural networks open the door to data mining techniques to play a major role in oil and gas industry. Unfortunately, the developed neural networks correlations are often limited, and global correlations are usually less accurate compared to local correlations. Recently, adaptive neuro-fuzzy inference systems have been proposed as a new intelligence framework for both prediction and classification based on fuzzy clustering optimization criterion and ranking. This paper proposes neuro-fuzzy inference systems for estimating PVT properties of crude oil systems. This new framework is an efficient hybrid intelligence machine learning scheme for modeling the kind of uncertainty associated with vagueness and imprecision. We briefly describe the learning steps and the use of the Takagi Sugeno and Kang model and Gustafson-Kessel clustering algorithm with K-detected clusters from the given database. It has featured in a wide range of medical, power control system, and business journals, often with promising results. A comparative study will be carried out to compare their performance of this new framework with the most popular modeling techniques, such as neural networks, nonlinear regression, and the empirical correlations algorithms. The results show that the performance of neuro-fuzzy systems is accurate, reliable, and outperform most of the existing forecasting techniques. Future work can be achieved by using neuro-fuzzy systems for clustering the 3D seismic data, identification of lithofacies types, and other reservoir characterization.
Multi-Scale Multi-Physics Modeling of Matrix Transport Properties in Fractured Shale Reservoirs

NASA Astrophysics Data System (ADS)

Mehmani, A.; Prodanovic, M.

2014-12-01

Understanding the shale matrix flow behavior is imperative in successful reservoir development for hydrocarbon production and carbon storage. Without a predictive model, significant uncertainties in flowback from the formation, the communication between the fracture and matrix as well as proper fracturing practice will ensue. Informed by SEM images, we develop deterministic network models that couple pores from multiple scales and their respective fluid physics. The models are used to investigate sorption hysteresis as an affordable way of inferring the nanoscale pore structure in core scale. In addition, restricted diffusion as a function of pore shape, pore-throat size ratios and network connectivity is computed to make correct interpretation of the 2D NMR maps possible. Our novel pore network models have the ability to match sorption hysteresis measurements without any tuning parameters. The results clarify a common misconception of linking type 3 nitrogen hysteresis curves to only the shale pore shape and show promising sensitivty for nanopore structre inference in core scale. The results on restricted diffusion shed light on the importance of including shape factors in 2D NMR interpretations. A priori "weighting factors" as a function of pore-throat and throat-length ratio are presented and the effect of network connectivity on diffusion is quantitatively assessed. We are currently working on verifying our models with experimental data gathered from the Eagleford formation.
Reasoning about Causal Relationships: Inferences on Causal Networks

PubMed Central

Rottman, Benjamin Margolin; Hastie, Reid

2013-01-01

Over the last decade, a normative framework for making causal inferences, Bayesian Probabilistic Causal Networks, has come to dominate psychological studies of inference based on causal relationships. The following causal networks—[X→Y→Z, X←Y→Z, X→Y←Z]—supply answers for questions like, “Suppose both X and Y occur, what is the probability Z occurs?” or “Suppose you intervene and make Y occur, what is the probability Z occurs?” In this review, we provide a tutorial for how normatively to calculate these inferences. Then, we systematically detail the results of behavioral studies comparing human qualitative and quantitative judgments to the normative calculations for many network structures and for several types of inferences on those networks. Overall, when the normative calculations imply that an inference should increase, judgments usually go up; when calculations imply a decrease, judgments usually go down. However, two systematic deviations appear. First, people’s inferences violate the Markov assumption. For example, when inferring Z from the structure X→Y→Z, people think that X is relevant even when Y completely mediates the relationship between X and Z. Second, even when people’s inferences are directionally consistent with the normative calculations, they are often not as sensitive to the parameters and the structure of the network as they should be. We conclude with a discussion of productive directions for future research. PMID:23544658
Inferring explicit weighted consensus networks to represent alternative evolutionary histories

PubMed Central

2013-01-01

Background The advent of molecular biology techniques and constant increase in availability of genetic material have triggered the development of many phylogenetic tree inference methods. However, several reticulate evolution processes, such as horizontal gene transfer and hybridization, have been shown to blur the species evolutionary history by causing discordance among phylogenies inferred from different genes. Methods To tackle this problem, we hereby describe a new method for inferring and representing alternative (reticulate) evolutionary histories of species as an explicit weighted consensus network which can be constructed from a collection of gene trees with or without prior knowledge of the species phylogeny. Results We provide a way of building a weighted phylogenetic network for each of the following reticulation mechanisms: diploid hybridization, intragenic recombination and complete or partial horizontal gene transfer. We successfully tested our method on some synthetic and real datasets to infer the above-mentioned evolutionary events which may have influenced the evolution of many species. Conclusions Our weighted consensus network inference method allows one to infer, visualize and validate statistically major conflicting signals induced by the mechanisms of reticulate evolution. The results provided by the new method can be used to represent the inferred conflicting signals by means of explicit and easy-to-interpret phylogenetic networks. PMID:24359207
Impact of biased scores on ranking in bipartite competition networks and inference of modular structure via generalized modularity

NASA Astrophysics Data System (ADS)

Jeon, Gyuhyeon; Park, Juyong

2017-02-01

In the common jury-contestant competition format, a jury consisting of multiple judges grade contestants on their performances to determine their ranking. Unlike in another common competition format where two contestants play a head-to-head match to produce the winner such as in football or basketball, the objectivity of judges are often called into question, potentially undermining the public's trust in the fairness of the competition. In this work we show, by modeling the jury-contestant competition format as a weighted bipartite network, how one can identify biased scores and how they impact the competition and its structure. Analyzing the prestigious International Chopin Piano Competition of 2015 as an example with a well-publicized scoring controversy, we show that the presence of even a very small fraction of biased edges can gravely distort our inference of the network structure —in the example a single biased edge is shown to lead to an incorrect “solution” that also wrongly appears to be robust exclusively, dominating other reasonable solutions— highlighting the importance of bias detection and elimination in network inference. In the process our work also presents a modified modularity measure for the one-mode projection of weighted complete bipartite networks.
A Predictive Approach to Network Reverse-Engineering

NASA Astrophysics Data System (ADS)

Wiggins, Chris

2005-03-01

A central challenge of systems biology is the ``reverse engineering" of transcriptional networks: inferring which genes exert regulatory control over which other genes. Attempting such inference at the genomic scale has only recently become feasible, via data-intensive biological innovations such as DNA microrrays (``DNA chips") and the sequencing of whole genomes. In this talk we present a predictive approach to network reverse-engineering, in which we integrate DNA chip data and sequence data to build a model of the transcriptional network of the yeast S. cerevisiae capable of predicting the response of genes in unseen experiments. The technique can also be used to extract ``motifs,'' sequence elements which act as binding sites for regulatory proteins. We validate by a number of approaches and present comparison of theoretical prediction vs. experimental data, along with biological interpretations of the resulting model. En route, we will illustrate some basic notions in statistical learning theory (fitting vs. over-fitting; cross- validation; assessing statistical significance), highlighting ways in which physicists can make a unique contribution in data- driven approaches to reverse engineering.
Multimodality Inferring of Human Cognitive States Based on Integration of Neuro-Fuzzy Network and Information Fusion Techniques

NASA Astrophysics Data System (ADS)

Yang, G.; Lin, Y.; Bhattacharya, P.

2007-12-01

To achieve an effective and safe operation on the machine system where the human interacts with the machine mutually, there is a need for the machine to understand the human state, especially cognitive state, when the human's operation task demands an intensive cognitive activity. Due to a well-known fact with the human being, a highly uncertain cognitive state and behavior as well as expressions or cues, the recent trend to infer the human state is to consider multimodality features of the human operator. In this paper, we present a method for multimodality inferring of human cognitive states by integrating neuro-fuzzy network and information fusion techniques. To demonstrate the effectiveness of this method, we take the driver fatigue detection as an example. The proposed method has, in particular, the following new features. First, human expressions are classified into four categories: (i) casual or contextual feature, (ii) contact feature, (iii) contactless feature, and (iv) performance feature. Second, the fuzzy neural network technique, in particular Takagi-Sugeno-Kang (TSK) model, is employed to cope with uncertain behaviors. Third, the sensor fusion technique, in particular ordered weighted aggregation (OWA), is integrated with the TSK model in such a way that cues are taken as inputs to the TSK model, and then the outputs of the TSK are fused by the OWA which gives outputs corresponding to particular cognitive states under interest (e.g., fatigue). We call this method TSK-OWA. Validation of the TSK-OWA, performed in the Northeastern University vehicle drive simulator, has shown that the proposed method is promising to be a general tool for human cognitive state inferring and a special tool for the driver fatigue detection.
Inferring Network Controls from Topology Using the Chomp Database

DTIC Science & Technology

2015-12-03

AFRL-AFOSR-VA-TR-2016-0033 INFERRING NETWORK CONTROLS FROM TOPOLOGY USING THE CHOMP DATABASE John Harer DUKE UNIVERSITY Final Report 12/03/2015...INFERRING NETWORK CONTROLS FROM TOPOLOGY USING THE CHOMP DATABASE 5a. CONTRACT NUMBER 5b. GRANT NUMBER FA9550-10-1-0436 5c. PROGRAM ELEMENT NUMBER 6...area of Topological Data Analysis (TDA) and it’s application to dynamical systems. The role of this work in the Complex Networks program is based on
Boolean dynamics of genetic regulatory networks inferred from microarray time series data

DOE PAGES

Martin, Shawn; Zhang, Zhaoduo; Martino, Anthony; ...

2007-01-31

Methods available for the inference of genetic regulatory networks strive to produce a single network, usually by optimizing some quantity to fit the experimental observations. In this paper we investigate the possibility that multiple networks can be inferred, all resulting in similar dynamics. This idea is motivated by theoretical work which suggests that biological networks are robust and adaptable to change, and that the overall behavior of a genetic regulatory network might be captured in terms of dynamical basins of attraction. We have developed and implemented a method for inferring genetic regulatory networks for time series microarray data. Our methodmore » first clusters and discretizes the gene expression data using k-means and support vector regression. We then enumerate Boolean activation–inhibition networks to match the discretized data. In conclusion, the dynamics of the Boolean networks are examined. We have tested our method on two immunology microarray datasets: an IL-2-stimulated T cell response dataset and a LPS-stimulated macrophage response dataset. In both cases, we discovered that many networks matched the data, and that most of these networks had similar dynamics.« less
Accuracy test for link prediction in terms of similarity index: The case of WS and BA models

NASA Astrophysics Data System (ADS)

Ahn, Min-Woo; Jung, Woo-Sung

2015-07-01

Link prediction is a technique that uses the topological information in a given network to infer the missing links in it. Since past research on link prediction has primarily focused on enhancing performance for given empirical systems, negligible attention has been devoted to link prediction with regard to network models. In this paper, we thus apply link prediction to two network models: The Watts-Strogatz (WS) model and Barabási-Albert (BA) model. We attempt to gain a better understanding of the relation between accuracy and each network parameter (mean degree, the number of nodes and the rewiring probability in the WS model) through network models. Six similarity indices are used, with precision and area under the ROC curve (AUC) value as the accuracy metrics. We observe a positive correlation between mean degree and accuracy, and size independence of the AUC value.
Deep Learning Fluid Mechanics

NASA Astrophysics Data System (ADS)

Barati Farimani, Amir; Gomes, Joseph; Pande, Vijay

2017-11-01

We have developed a new data-driven model paradigm for the rapid inference and solution of the constitutive equations of fluid mechanic by deep learning models. Using generative adversarial networks (GAN), we train models for the direct generation of solutions to steady state heat conduction and incompressible fluid flow without knowledge of the underlying governing equations. Rather than using artificial neural networks to approximate the solution of the constitutive equations, GANs can directly generate the solutions to these equations conditional upon an arbitrary set of boundary conditions. Both models predict temperature, velocity and pressure fields with great test accuracy (>99.5%). The application of our framework for inferring and generating the solutions of partial differential equations can be applied to any physical phenomena and can be used to learn directly from experiments where the underlying physical model is complex or unknown. We also have shown that our framework can be used to couple multiple physics simultaneously, making it amenable to tackle multi-physics problems.
fastBMA: scalable network inference and transitive reduction.

PubMed

Hung, Ling-Hong; Shi, Kaiyuan; Wu, Migao; Young, William Chad; Raftery, Adrian E; Yeung, Ka Yee

2017-10-01

Inferring genetic networks from genome-wide expression data is extremely demanding computationally. We have developed fastBMA, a distributed, parallel, and scalable implementation of Bayesian model averaging (BMA) for this purpose. fastBMA also includes a computationally efficient module for eliminating redundant indirect edges in the network by mapping the transitive reduction to an easily solved shortest-path problem. We evaluated the performance of fastBMA on synthetic data and experimental genome-wide time series yeast and human datasets. When using a single CPU core, fastBMA is up to 100 times faster than the next fastest method, LASSO, with increased accuracy. It is a memory-efficient, parallel, and distributed application that scales to human genome-wide expression data. A 10 000-gene regulation network can be obtained in a matter of hours using a 32-core cloud cluster (2 nodes of 16 cores). fastBMA is a significant improvement over its predecessor ScanBMA. It is more accurate and orders of magnitude faster than other fast network inference methods such as the 1 based on LASSO. The improved scalability allows it to calculate networks from genome scale data in a reasonable time frame. The transitive reduction method can improve accuracy in denser networks. fastBMA is available as code (M.I.T. license) from GitHub (https://github.com/lhhunghimself/fastBMA), as part of the updated networkBMA Bioconductor package (https://www.bioconductor.org/packages/release/bioc/html/networkBMA.html) and as ready-to-deploy Docker images (https://hub.docker.com/r/biodepot/fastbma/). © The Authors 2017. Published by Oxford University Press.
Hebbian Wiring Plasticity Generates Efficient Network Structures for Robust Inference with Synaptic Weight Plasticity

PubMed Central

Hiratani, Naoki; Fukai, Tomoki

2016-01-01

In the adult mammalian cortex, a small fraction of spines are created and eliminated every day, and the resultant synaptic connection structure is highly nonrandom, even in local circuits. However, it remains unknown whether a particular synaptic connection structure is functionally advantageous in local circuits, and why creation and elimination of synaptic connections is necessary in addition to rich synaptic weight plasticity. To answer these questions, we studied an inference task model through theoretical and numerical analyses. We demonstrate that a robustly beneficial network structure naturally emerges by combining Hebbian-type synaptic weight plasticity and wiring plasticity. Especially in a sparsely connected network, wiring plasticity achieves reliable computation by enabling efficient information transmission. Furthermore, the proposed rule reproduces experimental observed correlation between spine dynamics and task performance. PMID:27303271
Inference, simulation, modeling, and analysis of complex networks, with special emphasis on complex networks in systems biology

NASA Astrophysics Data System (ADS)

Christensen, Claire Petra

Across diverse fields ranging from physics to biology, sociology, and economics, the technological advances of the past decade have engendered an unprecedented explosion of data on highly complex systems with thousands, if not millions of interacting components. These systems exist at many scales of size and complexity, and it is becoming ever-more apparent that they are, in fact, universal, arising in every field of study. Moreover, they share fundamental properties---chief among these, that the individual interactions of their constituent parts may be well-understood, but the characteristic behaviour produced by the confluence of these interactions---by these complex networks---is unpredictable; in a nutshell, the whole is more than the sum of its parts. There is, perhaps, no better illustration of this concept than the discoveries being made regarding complex networks in the biological sciences. In particular, though the sequencing of the human genome in 2003 was a remarkable feat, scientists understand that the "cellular-level blueprints" for the human being are cellular-level parts lists, but they say nothing (explicitly) about cellular-level processes. The challenge of modern molecular biology is to understand these processes in terms of the networks of parts---in terms of the interactions among proteins, enzymes, genes, and metabolites---as it is these processes that ultimately differentiate animate from inanimate, giving rise to life! It is the goal of systems biology---an umbrella field encapsulating everything from molecular biology to epidemiology in social systems---to understand processes in terms of fundamental networks of core biological parts, be they proteins or people. By virtue of the fact that there are literally countless complex systems, not to mention tools and techniques used to infer, simulate, analyze, and model these systems, it is impossible to give a truly comprehensive account of the history and study of complex systems. The author's own publications have contributed network inference, simulation, modeling, and analysis methods to the much larger body of work in systems biology, and indeed, in network science. The aim of this thesis is therefore twofold: to present this original work in the historical context of network science, but also to provide sufficient review and reference regarding complex systems (with an emphasis on complex networks in systems biology) and tools and techniques for their inference, simulation, analysis, and modeling, such that the reader will be comfortable in seeking out further information on the subject. The review-like Chapters 1, 2, and 4 are intended to convey the co-evolution of network science and the slow but noticeable breakdown of boundaries between disciplines in academia as research and comparison of diverse systems has brought to light the shared properties of these systems. It is the author's hope that theses chapters impart some sense of the remarkable and rapid progress in complex systems research that has led to this unprecedented academic synergy. Chapters 3 and 5 detail the author's original work in the context of complex systems research. Chapter 3 presents the methods and results of a two-stage modeling process that generates candidate gene-regulatory networks of the bacterium B.subtilis from experimentally obtained, yet mathematically underdetermined microchip array data. These networks are then analyzed from a graph theoretical perspective, and their biological viability is critiqued by comparing the networks' graph theoretical properties to those of other biological systems. The results of topological perturbation analyses revealing commonalities in behavior at multiple levels of complexity are also presented, and are shown to be an invaluable means by which to ascertain the level of complexity to which the network inference process is robust to noise. Chapter 5 outlines a learning algorithm for the development of a realistic, evolving social network (a city) into which a disease is introduced. The results of simulations in populations spanning two orders of magnitude are compared to prevaccine era measles data for England and Wales and demonstrate that the simulations are able to capture the quantitative and qualitative features of epidemics in populations as small as 10,000 people. The work presented in Chapter 5 validates the utility of network simulation in concurrently probing contact network dynamics and disease dynamics.
Inferring Centrality from Network Snapshots

PubMed Central

Shao, Haibin; Mesbahi, Mehran; Li, Dewei; Xi, Yugeng

2017-01-01

The topology and dynamics of a complex network shape its functionality. However, the topologies of many large-scale networks are either unavailable or incomplete. Without the explicit knowledge of network topology, we show how the data generated from the network dynamics can be utilised to infer the tempo centrality, which is proposed to quantify the influence of nodes in a consensus network. We show that the tempo centrality can be used to construct an accurate estimate of both the propagation rate of influence exerted on consensus networks and the Kirchhoff index of the underlying graph. Moreover, the tempo centrality also encodes the disturbance rejection of nodes in a consensus network. Our findings provide an approach to infer the performance of a consensus network from its temporal data. PMID:28098166

Inferring Centrality from Network Snapshots

NASA Astrophysics Data System (ADS)

Shao, Haibin; Mesbahi, Mehran; Li, Dewei; Xi, Yugeng

2017-01-01

The topology and dynamics of a complex network shape its functionality. However, the topologies of many large-scale networks are either unavailable or incomplete. Without the explicit knowledge of network topology, we show how the data generated from the network dynamics can be utilised to infer the tempo centrality, which is proposed to quantify the influence of nodes in a consensus network. We show that the tempo centrality can be used to construct an accurate estimate of both the propagation rate of influence exerted on consensus networks and the Kirchhoff index of the underlying graph. Moreover, the tempo centrality also encodes the disturbance rejection of nodes in a consensus network. Our findings provide an approach to infer the performance of a consensus network from its temporal data.
Inferring the mesoscale structure of layered, edge-valued, and time-varying networks

NASA Astrophysics Data System (ADS)

Peixoto, Tiago P.

2015-10-01

Many network systems are composed of interdependent but distinct types of interactions, which cannot be fully understood in isolation. These different types of interactions are often represented as layers, attributes on the edges, or as a time dependence of the network structure. Although they are crucial for a more comprehensive scientific understanding, these representations offer substantial challenges. Namely, it is an open problem how to precisely characterize the large or mesoscale structure of network systems in relation to these additional aspects. Furthermore, the direct incorporation of these features invariably increases the effective dimension of the network description, and hence aggravates the problem of overfitting, i.e., the use of overly complex characterizations that mistake purely random fluctuations for actual structure. In this work, we propose a robust and principled method to tackle these problems, by constructing generative models of modular network structure, incorporating layered, attributed and time-varying properties, as well as a nonparametric Bayesian methodology to infer the parameters from data and select the most appropriate model according to statistical evidence. We show that the method is capable of revealing hidden structure in layered, edge-valued, and time-varying networks, and that the most appropriate level of granularity with respect to the additional dimensions can be reliably identified. We illustrate our approach on a variety of empirical systems, including a social network of physicians, the voting correlations of deputies in the Brazilian national congress, the global airport network, and a proximity network of high-school students.
Hydrological time series modeling: A comparison between adaptive neuro-fuzzy, neural network and autoregressive techniques

NASA Astrophysics Data System (ADS)

Lohani, A. K.; Kumar, Rakesh; Singh, R. D.

2012-06-01

SummaryTime series modeling is necessary for the planning and management of reservoirs. More recently, the soft computing techniques have been used in hydrological modeling and forecasting. In this study, the potential of artificial neural networks and neuro-fuzzy system in monthly reservoir inflow forecasting are examined by developing and comparing monthly reservoir inflow prediction models, based on autoregressive (AR), artificial neural networks (ANNs) and adaptive neural-based fuzzy inference system (ANFIS). To take care the effect of monthly periodicity in the flow data, cyclic terms are also included in the ANN and ANFIS models. Working with time series flow data of the Sutlej River at Bhakra Dam, India, several ANN and adaptive neuro-fuzzy models are trained with different input vectors. To evaluate the performance of the selected ANN and adaptive neural fuzzy inference system (ANFIS) models, comparison is made with the autoregressive (AR) models. The ANFIS model trained with the input data vector including previous inflows and cyclic terms of monthly periodicity has shown a significant improvement in the forecast accuracy in comparison with the ANFIS models trained with the input vectors considering only previous inflows. In all cases ANFIS gives more accurate forecast than the AR and ANN models. The proposed ANFIS model coupled with the cyclic terms is shown to provide better representation of the monthly inflow forecasting for planning and operation of reservoir.
Causal Inference and Explaining Away in a Spiking Network

PubMed Central

Moreno-Bote, Rubén; Drugowitsch, Jan

2015-01-01

While the brain uses spiking neurons for communication, theoretical research on brain computations has mostly focused on non-spiking networks. The nature of spike-based algorithms that achieve complex computations, such as object probabilistic inference, is largely unknown. Here we demonstrate that a family of high-dimensional quadratic optimization problems with non-negativity constraints can be solved exactly and efficiently by a network of spiking neurons. The network naturally imposes the non-negativity of causal contributions that is fundamental to causal inference, and uses simple operations, such as linear synapses with realistic time constants, and neural spike generation and reset non-linearities. The network infers the set of most likely causes from an observation using explaining away, which is dynamically implemented by spike-based, tuned inhibition. The algorithm performs remarkably well even when the network intrinsically generates variable spike trains, the timing of spikes is scrambled by external sources of noise, or the network is mistuned. This type of network might underlie tasks such as odor identification and classification. PMID:26621426
Causal Inference and Explaining Away in a Spiking Network.

PubMed

Moreno-Bote, Rubén; Drugowitsch, Jan

2015-12-01

While the brain uses spiking neurons for communication, theoretical research on brain computations has mostly focused on non-spiking networks. The nature of spike-based algorithms that achieve complex computations, such as object probabilistic inference, is largely unknown. Here we demonstrate that a family of high-dimensional quadratic optimization problems with non-negativity constraints can be solved exactly and efficiently by a network of spiking neurons. The network naturally imposes the non-negativity of causal contributions that is fundamental to causal inference, and uses simple operations, such as linear synapses with realistic time constants, and neural spike generation and reset non-linearities. The network infers the set of most likely causes from an observation using explaining away, which is dynamically implemented by spike-based, tuned inhibition. The algorithm performs remarkably well even when the network intrinsically generates variable spike trains, the timing of spikes is scrambled by external sources of noise, or the network is mistuned. This type of network might underlie tasks such as odor identification and classification.
ShinyKGode: an interactive application for ODE parameter inference using gradient matching.

PubMed

Wandy, Joe; Niu, Mu; Giurghita, Diana; Daly, Rónán; Rogers, Simon; Husmeier, Dirk

2018-07-01

Mathematical modelling based on ordinary differential equations (ODEs) is widely used to describe the dynamics of biological systems, particularly in systems and pathway biology. Often the kinetic parameters of these ODE systems are unknown and have to be inferred from the data. Approximate parameter inference methods based on gradient matching (which do not require performing computationally expensive numerical integration of the ODEs) have been getting popular in recent years, but many implementations are difficult to run without expert knowledge. Here, we introduce ShinyKGode, an interactive web application to perform fast parameter inference on ODEs using gradient matching. ShinyKGode can be used to infer ODE parameters on simulated and observed data using gradient matching. Users can easily load their own models in Systems Biology Markup Language format, and a set of pre-defined ODE benchmark models are provided in the application. Inferred parameters are visualized alongside diagnostic plots to assess convergence. The R package for ShinyKGode can be installed through the Comprehensive R Archive Network (CRAN). Installation instructions, as well as tutorial videos and source code are available at https://joewandy.github.io/shinyKGode. Supplementary data are available at Bioinformatics online.
From brain topography to brain topology: relevance of graph theory to functional neuroscience.

PubMed

Minati, Ludovico; Varotto, Giulia; D'Incerti, Ludovico; Panzica, Ferruccio; Chan, Dennis

2013-07-10

Although several brain regions show significant specialization, higher functions such as cross-modal information integration, abstract reasoning and conscious awareness are viewed as emerging from interactions across distributed functional networks. Analytical approaches capable of capturing the properties of such networks can therefore enhance our ability to make inferences from functional MRI, electroencephalography and magnetoencephalography data. Graph theory is a branch of mathematics that focuses on the formal modelling of networks and offers a wide range of theoretical tools to quantify specific features of network architecture (topology) that can provide information complementing the anatomical localization of areas responding to given stimuli or tasks (topography). Explicit modelling of the architecture of axonal connections and interactions among areas can furthermore reveal peculiar topological properties that are conserved across diverse biological networks, and highly sensitive to disease states. The field is evolving rapidly, partly fuelled by computational developments that enable the study of connectivity at fine anatomical detail and the simultaneous interactions among multiple regions. Recent publications in this area have shown that graph-based modelling can enhance our ability to draw causal inferences from functional MRI experiments, and support the early detection of disconnection and the modelling of pathology spread in neurodegenerative disease, particularly Alzheimer's disease. Furthermore, neurophysiological studies have shown that network topology has a profound link to epileptogenesis and that connectivity indices derived from graph models aid in modelling the onset and spread of seizures. Graph-based analyses may therefore significantly help understand the bases of a range of neurological conditions. This review is designed to provide an overview of graph-based analyses of brain connectivity and their relevance to disease aimed principally at general neuroscientists and clinicians.
Fast Inference of Deep Neural Networks in FPGAs for Particle Physics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duarte, Javier; Han, Song; Harris, Philip

Recent results at the Large Hadron Collider (LHC) have pointed to enhanced physics capabilities through the improvement of the real-time event processing techniques. Machine learning methods are ubiquitous and have proven to be very powerful in LHC physics, and particle physics as a whole. However, exploration of the use of such techniques in low-latency, low-power FPGA hardware has only just begun. FPGA-based trigger and data acquisition (DAQ) systems have extremely low, sub-microsecond latency requirements that are unique to particle physics. We present a case study for neural network inference in FPGAs focusing on a classifier for jet substructure which wouldmore » enable, among many other physics scenarios, searches for new dark sector particles and novel measurements of the Higgs boson. While we focus on a specific example, the lessons are far-reaching. We develop a package based on High-Level Synthesis (HLS) called hls4ml to build machine learning models in FPGAs. The use of HLS increases accessibility across a broad user community and allows for a drastic decrease in firmware development time. We map out FPGA resource usage and latency versus neural network hyperparameters to identify the problems in particle physics that would benefit from performing neural network inference with FPGAs. For our example jet substructure model, we fit well within the available resources of modern FPGAs with a latency on the scale of 100 ns.« less
Anomaly Detection in Dynamic Networks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Turcotte, Melissa

2014-10-14

Anomaly detection in dynamic communication networks has many important security applications. These networks can be extremely large and so detecting any changes in their structure can be computationally challenging; hence, computationally fast, parallelisable methods for monitoring the network are paramount. For this reason the methods presented here use independent node and edge based models to detect locally anomalous substructures within communication networks. As a first stage, the aim is to detect changes in the data streams arising from node or edge communications. Throughout the thesis simple, conjugate Bayesian models for counting processes are used to model these data streams. Amore » second stage of analysis can then be performed on a much reduced subset of the network comprising nodes and edges which have been identified as potentially anomalous in the first stage. The first method assumes communications in a network arise from an inhomogeneous Poisson process with piecewise constant intensity. Anomaly detection is then treated as a changepoint problem on the intensities. The changepoint model is extended to incorporate seasonal behavior inherent in communication networks. This seasonal behavior is also viewed as a changepoint problem acting on a piecewise constant Poisson process. In a static time frame, inference is made on this extended model via a Gibbs sampling strategy. In a sequential time frame, where the data arrive as a stream, a novel, fast Sequential Monte Carlo (SMC) algorithm is introduced to sample from the sequence of posterior distributions of the change points over time. A second method is considered for monitoring communications in a large scale computer network. The usage patterns in these types of networks are very bursty in nature and don’t fit a Poisson process model. For tractable inference, discrete time models are considered, where the data are aggregated into discrete time periods and probability models are fitted to the communication counts. In a sequential analysis, anomalous behavior is then identified from outlying behavior with respect to the fitted predictive probability models. Seasonality is again incorporated into the model and is treated as a changepoint model on the transition probabilities of a discrete time Markov process. Second stage analytics are then developed which combine anomalous edges to identify anomalous substructures in the network.« less
Python Environment for Bayesian Learning: Inferring the Structure of Bayesian Networks from Knowledge and Data

PubMed Central

Shah, Abhik; Woolf, Peter

2009-01-01

Summary In this paper, we introduce pebl, a Python library and application for learning Bayesian network structure from data and prior knowledge that provides features unmatched by alternative software packages: the ability to use interventional data, flexible specification of structural priors, modeling with hidden variables and exploitation of parallel processing. PMID:20161541
Inferring protein domains associated with drug side effects based on drug-target interaction network.

PubMed

Iwata, Hiroaki; Mizutani, Sayaka; Tabei, Yasuo; Kotera, Masaaki; Goto, Susumu; Yamanishi, Yoshihiro

2013-01-01

Most phenotypic effects of drugs are involved in the interactions between drugs and their target proteins, however, our knowledge about the molecular mechanism of the drug-target interactions is very limited. One of challenging issues in recent pharmaceutical science is to identify the underlying molecular features which govern drug-target interactions. In this paper, we make a systematic analysis of the correlation between drug side effects and protein domains, which we call "pharmacogenomic features," based on the drug-target interaction network. We detect drug side effects and protein domains that appear jointly in known drug-target interactions, which is made possible by using classifiers with sparse models. It is shown that the inferred pharmacogenomic features can be used for predicting potential drug-target interactions. We also discuss advantages and limitations of the pharmacogenomic features, compared with the chemogenomic features that are the associations between drug chemical substructures and protein domains. The inferred side effect-domain association network is expected to be useful for estimating common drug side effects for different protein families and characteristic drug side effects for specific protein domains.
Inference of Gene Regulatory Networks Using Bayesian Nonparametric Regression and Topology Information.

PubMed

Fan, Yue; Wang, Xiao; Peng, Qinke

2017-01-01

Gene regulatory networks (GRNs) play an important role in cellular systems and are important for understanding biological processes. Many algorithms have been developed to infer the GRNs. However, most algorithms only pay attention to the gene expression data but do not consider the topology information in their inference process, while incorporating this information can partially compensate for the lack of reliable expression data. Here we develop a Bayesian group lasso with spike and slab priors to perform gene selection and estimation for nonparametric models. B-spline basis functions are used to capture the nonlinear relationships flexibly and penalties are used to avoid overfitting. Further, we incorporate the topology information into the Bayesian method as a prior. We present the application of our method on DREAM3 and DREAM4 datasets and two real biological datasets. The results show that our method performs better than existing methods and the topology information prior can improve the result.
Incorporating time-delays in S-System model for reverse engineering genetic networks.

PubMed

Chowdhury, Ahsan Raja; Chetty, Madhu; Vinh, Nguyen Xuan

2013-06-18

In any gene regulatory network (GRN), the complex interactions occurring amongst transcription factors and target genes can be either instantaneous or time-delayed. However, many existing modeling approaches currently applied for inferring GRNs are unable to represent both these interactions simultaneously. As a result, all these approaches cannot detect important interactions of the other type. S-System model, a differential equation based approach which has been increasingly applied for modeling GRNs, also suffers from this limitation. In fact, all S-System based existing modeling approaches have been designed to capture only instantaneous interactions, and are unable to infer time-delayed interactions. In this paper, we propose a novel Time-Delayed S-System (TDSS) model which uses a set of delay differential equations to represent the system dynamics. The ability to incorporate time-delay parameters in the proposed S-System model enables simultaneous modeling of both instantaneous and time-delayed interactions. Furthermore, the delay parameters are not limited to just positive integer values (corresponding to time stamps in the data), but can also take fractional values. Moreover, we also propose a new criterion for model evaluation exploiting the sparse and scale-free nature of GRNs to effectively narrow down the search space, which not only reduces the computation time significantly but also improves model accuracy. The evaluation criterion systematically adapts the max-min in-degrees and also systematically balances the effect of network accuracy and complexity during optimization. The four well-known performance measures applied to the experimental studies on synthetic networks with various time-delayed regulations clearly demonstrate that the proposed method can capture both instantaneous and delayed interactions correctly with high precision. The experiments carried out on two well-known real-life networks, namely IRMA and SOS DNA repair network in Escherichia coli show a significant improvement compared with other state-of-the-art approaches for GRN modeling.
CompareSVM: supervised, Support Vector Machine (SVM) inference of gene regularity networks.

PubMed

Gillani, Zeeshan; Akash, Muhammad Sajid Hamid; Rahaman, M D Matiur; Chen, Ming

2014-11-30

Predication of gene regularity network (GRN) from expression data is a challenging task. There are many methods that have been developed to address this challenge ranging from supervised to unsupervised methods. Most promising methods are based on support vector machine (SVM). There is a need for comprehensive analysis on prediction accuracy of supervised method SVM using different kernels on different biological experimental conditions and network size. We developed a tool (CompareSVM) based on SVM to compare different kernel methods for inference of GRN. Using CompareSVM, we investigated and evaluated different SVM kernel methods on simulated datasets of microarray of different sizes in detail. The results obtained from CompareSVM showed that accuracy of inference method depends upon the nature of experimental condition and size of the network. For network with nodes (<200) and average (over all sizes of networks), SVM Gaussian kernel outperform on knockout, knockdown, and multifactorial datasets compared to all the other inference methods. For network with large number of nodes (~500), choice of inference method depend upon nature of experimental condition. CompareSVM is available at http://bis.zju.edu.cn/CompareSVM/ .
A building block for hardware belief networks.

PubMed

Behin-Aein, Behtash; Diep, Vinh; Datta, Supriyo

2016-07-21

Belief networks represent a powerful approach to problems involving probabilistic inference, but much of the work in this area is software based utilizing standard deterministic hardware based on the transistor which provides the gain and directionality needed to interconnect billions of them into useful networks. This paper proposes a transistor like device that could provide an analogous building block for probabilistic networks. We present two proof-of-concept examples of belief networks, one reciprocal and one non-reciprocal, implemented using the proposed device which is simulated using experimentally benchmarked models.
From molecular noise to behavioural variability in a single bacterium

NASA Astrophysics Data System (ADS)

Korobkova, Ekaterina; Emonet, Thierry; Vilar, Jose M. G.; Shimizu, Thomas S.; Cluzel, Philippe

2004-04-01

The chemotaxis network that governs the motion of Escherichia coli has long been studied to gain a general understanding of signal transduction. Although this pathway is composed of just a few components, it exhibits some essential characteristics of biological complexity, such as adaptation and response to environmental signals. In studying intracellular networks, most experiments and mathematical models have assumed that network properties can be inferred from population measurements. However, this approach masks underlying temporal fluctuations of intracellular signalling events. We have inferred fundamental properties of the chemotaxis network from a noise analysis of behavioural variations in individual bacteria. Here we show that certain properties established by population measurements, such as adapted states, are not conserved at the single-cell level: for timescales ranging from seconds to several minutes, the behaviour of non-stimulated cells exhibit temporal variations much larger than the expected statistical fluctuations. We find that the signalling network itself causes this noise and identify the molecular events that produce it. Small changes in the concentration of one key network component suppress temporal behavioural variability, suggesting that such variability is a selected property of this adaptive system.
Evidence Accumulation and Change Rate Inference in Dynamic Environments.

PubMed

Radillo, Adrian E; Veliz-Cuba, Alan; Josić, Krešimir; Kilpatrick, Zachary P

2017-06-01

In a constantly changing world, animals must account for environmental volatility when making decisions. To appropriately discount older, irrelevant information, they need to learn the rate at which the environment changes. We develop an ideal observer model capable of inferring the present state of the environment along with its rate of change. Key to this computation is an update of the posterior probability of all possible change point counts. This computation can be challenging, as the number of possibilities grows rapidly with time. However, we show how the computations can be simplified in the continuum limit by a moment closure approximation. The resulting low-dimensional system can be used to infer the environmental state and change rate with accuracy comparable to the ideal observer. The approximate computations can be performed by a neural network model via a rate-correlation-based plasticity rule. We thus show how optimal observers accumulate evidence in changing environments and map this computation to reduced models that perform inference using plausible neural mechanisms.
Maximally informative pairwise interactions in networks

PubMed Central

Fitzgerald, Jeffrey D.; Sharpee, Tatyana O.

2010-01-01

Several types of biological networks have recently been shown to be accurately described by a maximum entropy model with pairwise interactions, also known as the Ising model. Here we present an approach for finding the optimal mappings between input signals and network states that allow the network to convey the maximal information about input signals drawn from a given distribution. This mapping also produces a set of linear equations for calculating the optimal Ising-model coupling constants, as well as geometric properties that indicate the applicability of the pairwise Ising model. We show that the optimal pairwise interactions are on average zero for Gaussian and uniformly distributed inputs, whereas they are nonzero for inputs approximating those in natural environments. These nonzero network interactions are predicted to increase in strength as the noise in the response functions of each network node increases. This approach also suggests ways for how interactions with unmeasured parts of the network can be inferred from the parameters of response functions for the measured network nodes. PMID:19905153
Rethinking the learning of belief network probabilities

DOE Office of Scientific and Technical Information (OSTI.GOV)

Musick, R.

Belief networks are a powerful tool for knowledge discovery that provide concise, understandable probabilistic models of data. There are methods grounded in probability theory to incrementally update the relationships described by the belief network when new information is seen, to perform complex inferences over any set of variables in the data, to incorporate domain expertise and prior knowledge into the model, and to automatically learn the model from data. This paper concentrates on part of the belief network induction problem, that of learning the quantitative structure (the conditional probabilities), given the qualitative structure. In particular, the current practice of rotemore » learning the probabilities in belief networks can be significantly improved upon. We advance the idea of applying any learning algorithm to the task of conditional probability learning in belief networks, discuss potential benefits, and show results of applying neutral networks and other algorithms to a medium sized car insurance belief network. The results demonstrate from 10 to 100% improvements in model error rates over the current approaches.« less
Graphical models for optimal power flow

DOE PAGES

Dvijotham, Krishnamurthy; Chertkov, Michael; Van Hentenryck, Pascal; ...

2016-09-13

Optimal power flow (OPF) is the central optimization problem in electric power grids. Although solved routinely in the course of power grid operations, it is known to be strongly NP-hard in general, and weakly NP-hard over tree networks. In this paper, we formulate the optimal power flow problem over tree networks as an inference problem over a tree-structured graphical model where the nodal variables are low-dimensional vectors. We adapt the standard dynamic programming algorithm for inference over a tree-structured graphical model to the OPF problem. Combining this with an interval discretization of the nodal variables, we develop an approximation algorithmmore » for the OPF problem. Further, we use techniques from constraint programming (CP) to perform interval computations and adaptive bound propagation to obtain practically efficient algorithms. Compared to previous algorithms that solve OPF with optimality guarantees using convex relaxations, our approach is able to work for arbitrary tree-structured distribution networks and handle mixed-integer optimization problems. Further, it can be implemented in a distributed message-passing fashion that is scalable and is suitable for “smart grid” applications like control of distributed energy resources. In conclusion, numerical evaluations on several benchmark networks show that practical OPF problems can be solved effectively using this approach.« less

Nonlinear Inference in Partially Observed Physical Systems and Deep Neural Networks

NASA Astrophysics Data System (ADS)

Rozdeba, Paul J.

The problem of model state and parameter estimation is a significant challenge in nonlinear systems. Due to practical considerations of experimental design, it is often the case that physical systems are partially observed, meaning that data is only available for a subset of the degrees of freedom required to fully model the observed system's behaviors and, ultimately, predict future observations. Estimation in this context is highly complicated by the presence of chaos, stochasticity, and measurement noise in dynamical systems. One of the aims of this dissertation is to simultaneously analyze state and parameter estimation in as a regularized inverse problem, where the introduction of a model makes it possible to reverse the forward problem of partial, noisy observation; and as a statistical inference problem using data assimilation to transfer information from measurements to the model states and parameters. Ultimately these two formulations achieve the same goal. Similar aspects that appear in both are highlighted as a means for better understanding the structure of the nonlinear inference problem. An alternative approach to data assimilation that uses model reduction is then examined as a way to eliminate unresolved nonlinear gating variables from neuron models. In this formulation, only measured variables enter into the model, and the resulting errors are themselves modeled by nonlinear stochastic processes with memory. Finally, variational annealing, a data assimilation method previously applied to dynamical systems, is introduced as a potentially useful tool for understanding deep neural network training in machine learning by exploiting similarities between the two problems.
Super-Joule heating in graphene and silver nanowire network

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maize, Kerry; Das, Suprem R.; Sadeque, Sajia

Transistors, sensors, and transparent conductors based on randomly assembled nanowire networks rely on multi-component percolation for unique and distinctive applications in flexible electronics, biochemical sensing, and solar cells. While conduction models for 1-D and 1-D/2-D networks have been developed, typically assuming linear electronic transport and self-heating, the model has not been validated by direct high-resolution characterization of coupled electronic pathways and thermal response. In this letter, we show the occurrence of nonlinear “super-Joule” self-heating at the transport bottlenecks in networks of silver nanowires and silver nanowire/single layer graphene hybrid using high resolution thermoreflectance (TR) imaging. TR images at the microscopicmore » self-heating hotspots within nanowire network and nanowire/graphene hybrid network devices with submicron spatial resolution are used to infer electrical current pathways. The results encourage a fundamental reevaluation of transport models for network-based percolating conductors.« less
Functional Alignment of Metabolic Networks.

PubMed

Mazza, Arnon; Wagner, Allon; Ruppin, Eytan; Sharan, Roded

2016-05-01

Network alignment has become a standard tool in comparative biology, allowing the inference of protein function, interaction, and orthology. However, current alignment techniques are based on topological properties of networks and do not take into account their functional implications. Here we propose, for the first time, an algorithm to align two metabolic networks by taking advantage of their coupled metabolic models. These models allow us to assess the functional implications of genes or reactions, captured by the metabolic fluxes that are altered following their deletion from the network. Such implications may spread far beyond the region of the network where the gene or reaction lies. We apply our algorithm to align metabolic networks from various organisms, ranging from bacteria to humans, showing that our alignment can reveal functional orthology relations that are missed by conventional topological alignments.
Prioritising sewerage maintenance using inferred sewer age: a case study for Edinburgh.

PubMed

Arthur, S; Burkhard, R

2010-01-01

The reported research project focuses on using a database which contains details of customer contacts and CCTV data for a key Scottish catchment to construct a GIS based sewer condition model. Given the nature of the asset registry, a key research challenge was estimating the age of individual lengths of pipe. Within this context, asset age was inferred using the estimated age of surface developments-this involved overlaying the network in a GIS with historical digital maps. The paper illustrates that inferred asset age can reliably be used to highlight assets which are more likely to fail.
A Novel Adjustment Method for Shearer Traction Speed through Integration of T-S Cloud Inference Network and Improved PSO

PubMed Central

Si, Lei; Wang, Zhongbin; Yang, Yinwei

2014-01-01

In order to efficiently and accurately adjust the shearer traction speed, a novel approach based on Takagi-Sugeno (T-S) cloud inference network (CIN) and improved particle swarm optimization (IPSO) is proposed. The T-S CIN is built through the combination of cloud model and T-S fuzzy neural network. Moreover, the IPSO algorithm employs parameter automation adjustment strategy and velocity resetting to significantly improve the performance of basic PSO algorithm in global search and fine-tuning of the solutions, and the flowchart of proposed approach is designed. Furthermore, some simulation examples are carried out and comparison results indicate that the proposed method is feasible, efficient, and is outperforming others. Finally, an industrial application example of coal mining face is demonstrated to specify the effect of proposed system. PMID:25506358
An Architecture for Performance Optimization in a Collaborative Knowledge-Based Approach for Wireless Sensor Networks

PubMed Central

Gadeo-Martos, Manuel Angel; Fernandez-Prieto, Jose Angel; Canada-Bago, Joaquin; Velasco, Juan Ramon

2011-01-01

Over the past few years, Intelligent Spaces (ISs) have received the attention of many Wireless Sensor Network researchers. Recently, several studies have been devoted to identify their common capacities and to set up ISs over these networks. However, little attention has been paid to integrating Fuzzy Rule-Based Systems into collaborative Wireless Sensor Networks for the purpose of implementing ISs. This work presents a distributed architecture proposal for collaborative Fuzzy Rule-Based Systems embedded in Wireless Sensor Networks, which has been designed to optimize the implementation of ISs. This architecture includes the following: (a) an optimized design for the inference engine; (b) a visual interface; (c) a module to reduce the redundancy and complexity of the knowledge bases; (d) a module to evaluate the accuracy of the new knowledge base; (e) a module to adapt the format of the rules to the structure used by the inference engine; and (f) a communications protocol. As a real-world application of this architecture and the proposed methodologies, we show an application to the problem of modeling two plagues of the olive tree: prays (olive moth, Prays oleae Bern.) and repilo (caused by the fungus Spilocaea oleagina). The results show that the architecture presented in this paper significantly decreases the consumption of resources (memory, CPU and battery) without a substantial decrease in the accuracy of the inferred values. PMID:22163687
An architecture for performance optimization in a collaborative knowledge-based approach for wireless sensor networks.

PubMed

Gadeo-Martos, Manuel Angel; Fernandez-Prieto, Jose Angel; Canada-Bago, Joaquin; Velasco, Juan Ramon

2011-01-01

Over the past few years, Intelligent Spaces (ISs) have received the attention of many Wireless Sensor Network researchers. Recently, several studies have been devoted to identify their common capacities and to set up ISs over these networks. However, little attention has been paid to integrating Fuzzy Rule-Based Systems into collaborative Wireless Sensor Networks for the purpose of implementing ISs. This work presents a distributed architecture proposal for collaborative Fuzzy Rule-Based Systems embedded in Wireless Sensor Networks, which has been designed to optimize the implementation of ISs. This architecture includes the following: (a) an optimized design for the inference engine; (b) a visual interface; (c) a module to reduce the redundancy and complexity of the knowledge bases; (d) a module to evaluate the accuracy of the new knowledge base; (e) a module to adapt the format of the rules to the structure used by the inference engine; and (f) a communications protocol. As a real-world application of this architecture and the proposed methodologies, we show an application to the problem of modeling two plagues of the olive tree: prays (olive moth, Prays oleae Bern.) and repilo (caused by the fungus Spilocaea oleagina). The results show that the architecture presented in this paper significantly decreases the consumption of resources (memory, CPU and battery) without a substantial decrease in the accuracy of the inferred values.
Simultaneous learning of instantaneous and time-delayed genetic interactions using novel information theoretic scoring technique

PubMed Central

2012-01-01

Background Understanding gene interactions is a fundamental question in systems biology. Currently, modeling of gene regulations using the Bayesian Network (BN) formalism assumes that genes interact either instantaneously or with a certain amount of time delay. However in reality, biological regulations, both instantaneous and time-delayed, occur simultaneously. A framework that can detect and model both these two types of interactions simultaneously would represent gene regulatory networks more accurately. Results In this paper, we introduce a framework based on the Bayesian Network (BN) formalism that can represent both instantaneous and time-delayed interactions between genes simultaneously. A novel scoring metric having firm mathematical underpinnings is also proposed that, unlike other recent methods, can score both interactions concurrently and takes into account the reality that multiple regulators can regulate a gene jointly, rather than in an isolated pair-wise manner. Further, a gene regulatory network (GRN) inference method employing an evolutionary search that makes use of the framework and the scoring metric is also presented. Conclusion By taking into consideration the biological fact that both instantaneous and time-delayed regulations can occur among genes, our approach models gene interactions with greater accuracy. The proposed framework is efficient and can be used to infer gene networks having multiple orders of instantaneous and time-delayed regulations simultaneously. Experiments are carried out using three different synthetic networks (with three different mechanisms for generating synthetic data) as well as real life networks of Saccharomyces cerevisiae, E. coli and cyanobacteria gene expression data. The results show the effectiveness of our approach. PMID:22691450
MoCha: Molecular Characterization of Unknown Pathways.

PubMed

Lobo, Daniel; Hammelman, Jennifer; Levin, Michael

2016-04-01

Automated methods for the reverse-engineering of complex regulatory networks are paving the way for the inference of mechanistic comprehensive models directly from experimental data. These novel methods can infer not only the relations and parameters of the known molecules defined in their input datasets, but also unknown components and pathways identified as necessary by the automated algorithms. Identifying the molecular nature of these unknown components is a crucial step for making testable predictions and experimentally validating the models, yet no specific and efficient tools exist to aid in this process. To this end, we present here MoCha (Molecular Characterization), a tool optimized for the search of unknown proteins and their pathways from a given set of known interacting proteins. MoCha uses the comprehensive dataset of protein-protein interactions provided by the STRING database, which currently includes more than a billion interactions from over 2,000 organisms. MoCha is highly optimized, performing typical searches within seconds. We demonstrate the use of MoCha with the characterization of unknown components from reverse-engineered models from the literature. MoCha is useful for working on network models by hand or as a downstream step of a model inference engine workflow and represents a valuable and efficient tool for the characterization of unknown pathways using known data from thousands of organisms. MoCha and its source code are freely available online under the GPLv3 license.
Bayes Nets in Educational Assessment: Where Do the Numbers Come from? CSE Technical Report.

ERIC Educational Resources Information Center

Mislevy, Robert J.; Almond, Russell G.; Yan, Duanli; Steinberg, Linda S.

Educational assessments that exploit advances in technology and cognitive psychology can produce observations and pose student models that outstrip familiar test-theoretic models and analytic methods. Bayesian inference networks (BINs), which include familiar models and techniques as special cases, can be used to manage belief about students'…
Infering and Calibrating Triadic Closure in a Dynamic Network

NASA Astrophysics Data System (ADS)

Mantzaris, Alexander V.; Higham, Desmond J.

In the social sciences, the hypothesis of triadic closure contends that new links in a social contact network arise preferentially between those who currently share neighbours. Here, in a proof-of-principle study, we show how to calibrate a recently proposed evolving network model to time-dependent connectivity data. The probabilistic edge birth rate in the model contains a triadic closure term, so we are also able to assess statistically the evidence for this effect. The approach is shown to work on data generated synthetically from the model. We then apply this methodology to some real, large-scale data that records the build up of connections in a business-related social networking site, and find evidence for triadic closure.
Griffin: A Tool for Symbolic Inference of Synchronous Boolean Molecular Networks.

PubMed

Muñoz, Stalin; Carrillo, Miguel; Azpeitia, Eugenio; Rosenblueth, David A

2018-01-01

Boolean networks are important models of biochemical systems, located at the high end of the abstraction spectrum. A number of Boolean gene networks have been inferred following essentially the same method. Such a method first considers experimental data for a typically underdetermined "regulation" graph. Next, Boolean networks are inferred by using biological constraints to narrow the search space, such as a desired set of (fixed-point or cyclic) attractors. We describe Griffin , a computer tool enhancing this method. Griffin incorporates a number of well-established algorithms, such as Dubrova and Teslenko's algorithm for finding attractors in synchronous Boolean networks. In addition, a formal definition of regulation allows Griffin to employ "symbolic" techniques, able to represent both large sets of network states and Boolean constraints. We observe that when the set of attractors is required to be an exact set, prohibiting additional attractors, a naive Boolean coding of this constraint may be unfeasible. Such cases may be intractable even with symbolic methods, as the number of Boolean constraints may be astronomically large. To overcome this problem, we employ an Artificial Intelligence technique known as "clause learning" considerably increasing Griffin 's scalability. Without clause learning only toy examples prohibiting additional attractors are solvable: only one out of seven queries reported here is answered. With clause learning, by contrast, all seven queries are answered. We illustrate Griffin with three case studies drawn from the Arabidopsis thaliana literature. Griffin is available at: http://turing.iimas.unam.mx/griffin.
MINER: exploratory analysis of gene interaction networks by machine learning from expression data.

PubMed

Kadupitige, Sidath Randeni; Leung, Kin Chun; Sellmeier, Julia; Sivieng, Jane; Catchpoole, Daniel R; Bain, Michael E; Gaëta, Bruno A

2009-12-03

The reconstruction of gene regulatory networks from high-throughput "omics" data has become a major goal in the modelling of living systems. Numerous approaches have been proposed, most of which attempt only "one-shot" reconstruction of the whole network with no intervention from the user, or offer only simple correlation analysis to infer gene dependencies. We have developed MINER (Microarray Interactive Network Exploration and Representation), an application that combines multivariate non-linear tree learning of individual gene regulatory dependencies, visualisation of these dependencies as both trees and networks, and representation of known biological relationships based on common Gene Ontology annotations. MINER allows biologists to explore the dependencies influencing the expression of individual genes in a gene expression data set in the form of decision, model or regression trees, using their domain knowledge to guide the exploration and formulate hypotheses. Multiple trees can then be summarised in the form of a gene network diagram. MINER is being adopted by several of our collaborators and has already led to the discovery of a new significant regulatory relationship with subsequent experimental validation. Unlike most gene regulatory network inference methods, MINER allows the user to start from genes of interest and build the network gene-by-gene, incorporating domain expertise in the process. This approach has been used successfully with RNA microarray data but is applicable to other quantitative data produced by high-throughput technologies such as proteomics and "next generation" DNA sequencing.
Statistical Inference and Reverse Engineering of Gene Regulatory Networks from Observational Expression Data

PubMed Central

Emmert-Streib, Frank; Glazko, Galina V.; Altay, Gökmen; de Matos Simoes, Ricardo

2012-01-01

In this paper, we present a systematic and conceptual overview of methods for inferring gene regulatory networks from observational gene expression data. Further, we discuss two classic approaches to infer causal structures and compare them with contemporary methods by providing a conceptual categorization thereof. We complement the above by surveying global and local evaluation measures for assessing the performance of inference algorithms. PMID:22408642
Differentiable cortical networks for inferences concerning people’s intentions versus physical causality

PubMed Central

Mason, Robert A.; Just, Marcel Adam

2010-01-01

Cortical activity associated with generating an inference was measured using fMRI. Participants read three-sentence passages that differed in whether or not an inference needed to be drawn to understand them. The inference was based on either a protagonist’s intention or a physical consequence of a character’s action. Activation was expected in Theory of Mind brain regions for the passages based on protagonists’ intentions but not for the physical consequence passages. The activation measured in the right temporo-parietal junction was greater in the intentional passages than in the consequence passages, consistent with predictions from a Theory of Mind perspective. In contrast, there was increased occipital activation in the physical inference passages. For both types of passage, the cortical activity related to the reading of the critical inference sentence demonstrated a recruitment of a common inference cortical network. This general inference-related activation appeared bilaterally in the language processing areas (the inferior frontal gyrus, the temporal gyrus, and the angular gyrus), as well as in the medial to superior frontal gyrus, which has been found to be active in Theory of Mind tasks. These findings are consistent with the hypothesis that component areas of the discourse processing network are recruited as needed based on the nature of the inference. A Protagonist monitoring and synthesis network is proposed as a more accurate account for Theory of Mind activation during narrative comprehension. PMID:21229617
Clinical Outcome Prediction in Aneurysmal Subarachnoid Hemorrhage Using Bayesian Neural Networks with Fuzzy Logic Inferences

PubMed Central

Lo, Benjamin W. Y.; Macdonald, R. Loch; Baker, Andrew; Levine, Mitchell A. H.

2013-01-01

Objective. The novel clinical prediction approach of Bayesian neural networks with fuzzy logic inferences is created and applied to derive prognostic decision rules in cerebral aneurysmal subarachnoid hemorrhage (aSAH). Methods. The approach of Bayesian neural networks with fuzzy logic inferences was applied to data from five trials of Tirilazad for aneurysmal subarachnoid hemorrhage (3551 patients). Results. Bayesian meta-analyses of observational studies on aSAH prognostic factors gave generalizable posterior distributions of population mean log odd ratios (ORs). Similar trends were noted in Bayesian and linear regression ORs. Significant outcome predictors include normal motor response, cerebral infarction, history of myocardial infarction, cerebral edema, history of diabetes mellitus, fever on day 8, prior subarachnoid hemorrhage, admission angiographic vasospasm, neurological grade, intraventricular hemorrhage, ruptured aneurysm size, history of hypertension, vasospasm day, age and mean arterial pressure. Heteroscedasticity was present in the nontransformed dataset. Artificial neural networks found nonlinear relationships with 11 hidden variables in 1 layer, using the multilayer perceptron model. Fuzzy logic decision rules (centroid defuzzification technique) denoted cut-off points for poor prognosis at greater than 2.5 clusters. Discussion. This aSAH prognostic system makes use of existing knowledge, recognizes unknown areas, incorporates one's clinical reasoning, and compensates for uncertainty in prognostication. PMID:23690884
Transmission network of the 2014-2015 Ebola epidemic in Sierra Leone.

PubMed

Yang, Wan; Zhang, Wenyi; Kargbo, David; Yang, Ruifu; Chen, Yong; Chen, Zeliang; Kamara, Abdul; Kargbo, Brima; Kandula, Sasikiran; Karspeck, Alicia; Liu, Chao; Shaman, Jeffrey

2015-11-06

Understanding the growth and spatial expansion of (re)emerging infectious disease outbreaks, such as Ebola and avian influenza, is critical for the effective planning of control measures; however, such efforts are often compromised by data insufficiencies and observational errors. Here, we develop a spatial-temporal inference methodology using a modified network model in conjunction with the ensemble adjustment Kalman filter, a Bayesian inference method equipped to handle observational errors. The combined method is capable of revealing the spatial-temporal progression of infectious disease, while requiring only limited, readily compiled data. We use this method to reconstruct the transmission network of the 2014-2015 Ebola epidemic in Sierra Leone and identify source and sink regions. Our inference suggests that, in Sierra Leone, transmission within the network introduced Ebola to neighbouring districts and initiated self-sustaining local epidemics; two of the more populous and connected districts, Kenema and Port Loko, facilitated two independent transmission pathways. Epidemic intensity differed by district, was highly correlated with population size (r = 0.76, p = 0.0015) and a critical window of opportunity for containing local Ebola epidemics at the source (ca one month) existed. This novel methodology can be used to help identify and contain the spatial expansion of future (re)emerging infectious disease outbreaks. © 2015 The Author(s).
Robust Inference of Genetic Exchange Communities from Microbial Genomes Using TF-IDF.

PubMed

Cong, Yingnan; Chan, Yao-Ban; Phillips, Charles A; Langston, Michael A; Ragan, Mark A

2017-01-01

Bacteria and archaea can exchange genetic material across lineages through processes of lateral genetic transfer (LGT). Collectively, these exchange relationships can be modeled as a network and analyzed using concepts from graph theory. In particular, densely connected regions within an LGT network have been defined as genetic exchange communities (GECs). However, it has been problematic to construct networks in which edges solely represent LGT. Here we apply term frequency-inverse document frequency (TF-IDF), an alignment-free method originating from document analysis, to infer regions of lateral origin in bacterial genomes. We examine four empirical datasets of different size (number of genomes) and phyletic breadth, varying a key parameter (word length k ) within bounds established in previous work. We map the inferred lateral regions to genes in recipient genomes, and construct networks in which the nodes are groups of genomes, and the edges natively represent LGT. We then extract maximum and maximal cliques (i.e., GECs) from these graphs, and identify nodes that belong to GECs across a wide range of k . Most surviving lateral transfer has happened within these GECs. Using Gene Ontology enrichment tests we demonstrate that biological processes associated with metabolism, regulation and transport are often over-represented among the genes affected by LGT within these communities. These enrichments are largely robust to change of k .
Analysis of the GRNs Inference by Using Tsallis Entropy and a Feature Selection Approach

NASA Astrophysics Data System (ADS)

Lopes, Fabrício M.; de Oliveira, Evaldo A.; Cesar, Roberto M.

An important problem in the bioinformatics field is to understand how genes are regulated and interact through gene networks. This knowledge can be helpful for many applications, such as disease treatment design and drugs creation purposes. For this reason, it is very important to uncover the functional relationship among genes and then to construct the gene regulatory network (GRN) from temporal expression data. However, this task usually involves data with a large number of variables and small number of observations. In this way, there is a strong motivation to use pattern recognition and dimensionality reduction approaches. In particular, feature selection is specially important in order to select the most important predictor genes that can explain some phenomena associated with the target genes. This work presents a first study about the sensibility of entropy methods regarding the entropy functional form, applied to the problem of topology recovery of GRNs. The generalized entropy proposed by Tsallis is used to study this sensibility. The inference process is based on a feature selection approach, which is applied to simulated temporal expression data generated by an artificial gene network (AGN) model. The inferred GRNs are validated in terms of global network measures. Some interesting conclusions can be drawn from the experimental results, as reported for the first time in the present paper.
Proteomic Screening and Lasso Regression Reveal Differential Signaling in Insulin and Insulin-like Growth Factor I (IGF1) Pathways *

PubMed Central

Erdem, Cemal; Nagle, Alison M.; Casa, Angelo J.; Litzenburger, Beate C.; Wang, Yu-fen; Taylor, D. Lansing; Lee, Adrian V.; Lezon, Timothy R.

2016-01-01

Insulin and insulin-like growth factor I (IGF1) influence cancer risk and progression through poorly understood mechanisms. To better understand the roles of insulin and IGF1 signaling in breast cancer, we combined proteomic screening with computational network inference to uncover differences in IGF1 and insulin induced signaling. Using reverse phase protein array, we measured the levels of 134 proteins in 21 breast cancer cell lines stimulated with IGF1 or insulin for up to 48 h. We then constructed directed protein expression networks using three separate methods: (i) lasso regression, (ii) conventional matrix inversion, and (iii) entropy maximization. These networks, named here as the time translation models, were analyzed and the inferred interactions were ranked by differential magnitude to identify pathway differences. The two top candidates, chosen for experimental validation, were shown to regulate IGF1/insulin induced phosphorylation events. First, acetyl-CoA carboxylase (ACC) knock-down was shown to increase the level of mitogen-activated protein kinase (MAPK) phosphorylation. Second, stable knock-down of E-Cadherin increased the phospho-Akt protein levels. Both of the knock-down perturbations incurred phosphorylation responses stronger in IGF1 stimulated cells compared with insulin. Overall, the time-translation modeling coupled to wet-lab experiments has proven to be powerful in inferring differential interactions downstream of IGF1 and insulin signaling, in vitro. PMID:27364358

Influence of reciprocal edges on degree distribution and degree correlations

NASA Astrophysics Data System (ADS)

Zlatić, Vinko; Štefančić, Hrvoje

2009-07-01

Reciprocal edges represent the lowest-order cycle possible to find in directed graphs without self-loops. Representing also a measure of feedback between vertices, it is interesting to understand how reciprocal edges influence other properties of complex networks. In this paper, we focus on the influence of reciprocal edges on vertex degree distribution and degree correlations. We show that there is a fundamental difference between properties observed on the static network compared to the properties of networks, which are obtained by simple evolution mechanism driven by reciprocity. We also present a way to statistically infer the portion of reciprocal edges, which can be explained as a consequence of feedback process on the static network. In the rest of the paper, the influence of reciprocal edges on a model of growing network is also presented. It is shown that our model of growing network nicely interpolates between Barabási-Albert (BA) model for undirected and the BA model for directed networks.
Model criticism based on likelihood-free inference, with an application to protein network evolution.

PubMed

Ratmann, Oliver; Andrieu, Christophe; Wiuf, Carsten; Richardson, Sylvia

2009-06-30

Mathematical models are an important tool to explain and comprehend complex phenomena, and unparalleled computational advances enable us to easily explore them without any or little understanding of their global properties. In fact, the likelihood of the data under complex stochastic models is often analytically or numerically intractable in many areas of sciences. This makes it even more important to simultaneously investigate the adequacy of these models-in absolute terms, against the data, rather than relative to the performance of other models-but no such procedure has been formally discussed when the likelihood is intractable. We provide a statistical interpretation to current developments in likelihood-free Bayesian inference that explicitly accounts for discrepancies between the model and the data, termed Approximate Bayesian Computation under model uncertainty (ABCmicro). We augment the likelihood of the data with unknown error terms that correspond to freely chosen checking functions, and provide Monte Carlo strategies for sampling from the associated joint posterior distribution without the need of evaluating the likelihood. We discuss the benefit of incorporating model diagnostics within an ABC framework, and demonstrate how this method diagnoses model mismatch and guides model refinement by contrasting three qualitative models of protein network evolution to the protein interaction datasets of Helicobacter pylori and Treponema pallidum. Our results make a number of model deficiencies explicit, and suggest that the T. pallidum network topology is inconsistent with evolution dominated by link turnover or lateral gene transfer alone.
A Component-Based Diffusion Model With Structural Diversity for Social Networks.

PubMed

Qing Bao; Cheung, William K; Yu Zhang; Jiming Liu

2017-04-01

Diffusion on social networks refers to the process where opinions are spread via the connected nodes. Given a set of observed information cascades, one can infer the underlying diffusion process for social network analysis. The independent cascade model (IC model) is a widely adopted diffusion model where a node is assumed to be activated independently by any one of its neighbors. In reality, how a node will be activated also depends on how its neighbors are connected and activated. For instance, the opinions from the neighbors of the same social group are often similar and thus redundant. In this paper, we extend the IC model by considering that: 1) the information coming from the connected neighbors are similar and 2) the underlying redundancy can be modeled using a dynamic structural diversity measure of the neighbors. Our proposed model assumes each node to be activated independently by different communities (or components) of its parent nodes, each weighted by its effective size. An expectation maximization algorithm is derived to infer the model parameters. We compare the performance of the proposed model with the basic IC model and its variants using both synthetic data sets and a real-world data set containing news stories and Web blogs. Our empirical results show that incorporating the community structure of neighbors and the structural diversity measure into the diffusion model significantly improves the accuracy of the model, at the expense of only a reasonable increase in run-time.
Reverse engineering gene regulatory networks from measurement with missing values.

PubMed

Ogundijo, Oyetunji E; Elmas, Abdulkadir; Wang, Xiaodong

2016-12-01

Gene expression time series data are usually in the form of high-dimensional arrays. Unfortunately, the data may sometimes contain missing values: for either the expression values of some genes at some time points or the entire expression values of a single time point or some sets of consecutive time points. This significantly affects the performance of many algorithms for gene expression analysis that take as an input, the complete matrix of gene expression measurement. For instance, previous works have shown that gene regulatory interactions can be estimated from the complete matrix of gene expression measurement. Yet, till date, few algorithms have been proposed for the inference of gene regulatory network from gene expression data with missing values. We describe a nonlinear dynamic stochastic model for the evolution of gene expression. The model captures the structural, dynamical, and the nonlinear natures of the underlying biomolecular systems. We present point-based Gaussian approximation (PBGA) filters for joint state and parameter estimation of the system with one-step or two-step missing measurements . The PBGA filters use Gaussian approximation and various quadrature rules, such as the unscented transform (UT), the third-degree cubature rule and the central difference rule for computing the related posteriors. The proposed algorithm is evaluated with satisfying results for synthetic networks, in silico networks released as a part of the DREAM project, and the real biological network, the in vivo reverse engineering and modeling assessment (IRMA) network of yeast Saccharomyces cerevisiae . PBGA filters are proposed to elucidate the underlying gene regulatory network (GRN) from time series gene expression data that contain missing values. In our state-space model, we proposed a measurement model that incorporates the effect of the missing data points into the sequential algorithm. This approach produces a better inference of the model parameters and hence, more accurate prediction of the underlying GRN compared to when using the conventional Gaussian approximation (GA) filters ignoring the missing data points.
Augmenting Microarray Data with Literature-Based Knowledge to Enhance Gene Regulatory Network Inference

PubMed Central

Kilicoglu, Halil; Shin, Dongwook; Rindflesch, Thomas C.

2014-01-01

Gene regulatory networks are a crucial aspect of systems biology in describing molecular mechanisms of the cell. Various computational models rely on random gene selection to infer such networks from microarray data. While incorporation of prior knowledge into data analysis has been deemed important, in practice, it has generally been limited to referencing genes in probe sets and using curated knowledge bases. We investigate the impact of augmenting microarray data with semantic relations automatically extracted from the literature, with the view that relations encoding gene/protein interactions eliminate the need for random selection of components in non-exhaustive approaches, producing a more accurate model of cellular behavior. A genetic algorithm is then used to optimize the strength of interactions using microarray data and an artificial neural network fitness function. The result is a directed and weighted network providing the individual contribution of each gene to its target. For testing, we used invasive ductile carcinoma of the breast to query the literature and a microarray set containing gene expression changes in these cells over several time points. Our model demonstrates significantly better fitness than the state-of-the-art model, which relies on an initial random selection of genes. Comparison to the component pathways of the KEGG Pathways in Cancer map reveals that the resulting networks contain both known and novel relationships. The p53 pathway results were manually validated in the literature. 60% of non-KEGG relationships were supported (74% for highly weighted interactions). The method was then applied to yeast data and our model again outperformed the comparison model. Our results demonstrate the advantage of combining gene interactions extracted from the literature in the form of semantic relations with microarray analysis in generating contribution-weighted gene regulatory networks. This methodology can make a significant contribution to understanding the complex interactions involved in cellular behavior and molecular physiology. PMID:24921649
Augmenting microarray data with literature-based knowledge to enhance gene regulatory network inference.

PubMed

Chen, Guocai; Cairelli, Michael J; Kilicoglu, Halil; Shin, Dongwook; Rindflesch, Thomas C

2014-06-01

Gene regulatory networks are a crucial aspect of systems biology in describing molecular mechanisms of the cell. Various computational models rely on random gene selection to infer such networks from microarray data. While incorporation of prior knowledge into data analysis has been deemed important, in practice, it has generally been limited to referencing genes in probe sets and using curated knowledge bases. We investigate the impact of augmenting microarray data with semantic relations automatically extracted from the literature, with the view that relations encoding gene/protein interactions eliminate the need for random selection of components in non-exhaustive approaches, producing a more accurate model of cellular behavior. A genetic algorithm is then used to optimize the strength of interactions using microarray data and an artificial neural network fitness function. The result is a directed and weighted network providing the individual contribution of each gene to its target. For testing, we used invasive ductile carcinoma of the breast to query the literature and a microarray set containing gene expression changes in these cells over several time points. Our model demonstrates significantly better fitness than the state-of-the-art model, which relies on an initial random selection of genes. Comparison to the component pathways of the KEGG Pathways in Cancer map reveals that the resulting networks contain both known and novel relationships. The p53 pathway results were manually validated in the literature. 60% of non-KEGG relationships were supported (74% for highly weighted interactions). The method was then applied to yeast data and our model again outperformed the comparison model. Our results demonstrate the advantage of combining gene interactions extracted from the literature in the form of semantic relations with microarray analysis in generating contribution-weighted gene regulatory networks. This methodology can make a significant contribution to understanding the complex interactions involved in cellular behavior and molecular physiology.
Mobility timing for agent communities, a cue for advanced connectionist systems.

PubMed

Apolloni, Bruno; Bassis, Simone; Pagani, Elena; Rossi, Gian Paolo; Valerio, Lorenzo

2011-12-01

We introduce a wait-and-chase scheme that models the contact times between moving agents within a connectionist construct. The idea that elementary processors move within a network to get a proper position is borne out both by biological neurons in the brain morphogenesis and by agents within social networks. From the former, we take inspiration to devise a medium-term project for new artificial neural network training procedures where mobile neurons exchange data only when they are close to one another in a proper space (are in contact). From the latter, we accumulate mobility tracks experience. We focus on the preliminary step of characterizing the elapsed time between neuron contacts, which results from a spatial process fitting in the family of random processes with memory, where chasing neurons are stochastically driven by the goal of hitting target neurons. Thus, we add an unprecedented mobility model to the literature in the field, introducing a distribution law of the intercontact times that merges features of both negative exponential and Pareto distribution laws. We give a constructive description and implementation of our model, as well as a short analytical form whose parameters are suitably estimated in terms of confidence intervals from experimental data. Numerical experiments show the model and related inference tools to be sufficiently robust to cope with two main requisites for its exploitation in a neural network: the nonindependence of the observed intercontact times and the feasibility of the model inversion problem to infer suitable mobility parameters.
Identifying Keystone Species in the Human Gut Microbiome from Metagenomic Timeseries Using Sparse Linear Regression

PubMed Central

Fisher, Charles K.; Mehta, Pankaj

2014-01-01

Human associated microbial communities exert tremendous influence over human health and disease. With modern metagenomic sequencing methods it is now possible to follow the relative abundance of microbes in a community over time. These microbial communities exhibit rich ecological dynamics and an important goal of microbial ecology is to infer the ecological interactions between species directly from sequence data. Any algorithm for inferring ecological interactions must overcome three major obstacles: 1) a correlation between the abundances of two species does not imply that those species are interacting, 2) the sum constraint on the relative abundances obtained from metagenomic studies makes it difficult to infer the parameters in timeseries models, and 3) errors due to experimental uncertainty, or mis-assignment of sequencing reads into operational taxonomic units, bias inferences of species interactions due to a statistical problem called “errors-in-variables”. Here we introduce an approach, Learning Interactions from MIcrobial Time Series (LIMITS), that overcomes these obstacles. LIMITS uses sparse linear regression with boostrap aggregation to infer a discrete-time Lotka-Volterra model for microbial dynamics. We tested LIMITS on synthetic data and showed that it could reliably infer the topology of the inter-species ecological interactions. We then used LIMITS to characterize the species interactions in the gut microbiomes of two individuals and found that the interaction networks varied significantly between individuals. Furthermore, we found that the interaction networks of the two individuals are dominated by distinct “keystone species”, Bacteroides fragilis and Bacteroided stercosis, that have a disproportionate influence on the structure of the gut microbiome even though they are only found in moderate abundance. Based on our results, we hypothesize that the abundances of certain keystone species may be responsible for individuality in the human gut microbiome. PMID:25054627
Integrated Module and Gene-Specific Regulatory Inference Implicates Upstream Signaling Networks

PubMed Central

Roy, Sushmita; Lagree, Stephen; Hou, Zhonggang; Thomson, James A.; Stewart, Ron; Gasch, Audrey P.

2013-01-01

Regulatory networks that control gene expression are important in diverse biological contexts including stress response and development. Each gene's regulatory program is determined by module-level regulation (e.g. co-regulation via the same signaling system), as well as gene-specific determinants that can fine-tune expression. We present a novel approach, Modular regulatory network learning with per gene information (MERLIN), that infers regulatory programs for individual genes while probabilistically constraining these programs to reveal module-level organization of regulatory networks. Using edge-, regulator- and module-based comparisons of simulated networks of known ground truth, we find MERLIN reconstructs regulatory programs of individual genes as well or better than existing approaches of network reconstruction, while additionally identifying modular organization of the regulatory networks. We use MERLIN to dissect global transcriptional behavior in two biological contexts: yeast stress response and human embryonic stem cell differentiation. Regulatory modules inferred by MERLIN capture co-regulatory relationships between signaling proteins and downstream transcription factors thereby revealing the upstream signaling systems controlling transcriptional responses. The inferred networks are enriched for regulators with genetic or physical interactions, supporting the inference, and identify modules of functionally related genes bound by the same transcriptional regulators. Our method combines the strengths of per-gene and per-module methods to reveal new insights into transcriptional regulation in stress and development. PMID:24146602
Transcriptional network inference from functional similarity and expression data: a global supervised approach.

PubMed

Ambroise, Jérôme; Robert, Annie; Macq, Benoit; Gala, Jean-Luc

2012-01-06

An important challenge in system biology is the inference of biological networks from postgenomic data. Among these biological networks, a gene transcriptional regulatory network focuses on interactions existing between transcription factors (TFs) and and their corresponding target genes. A large number of reverse engineering algorithms were proposed to infer such networks from gene expression profiles, but most current methods have relatively low predictive performances. In this paper, we introduce the novel TNIFSED method (Transcriptional Network Inference from Functional Similarity and Expression Data), that infers a transcriptional network from the integration of correlations and partial correlations of gene expression profiles and gene functional similarities through a supervised classifier. In the current work, TNIFSED was applied to predict the transcriptional network in Escherichia coli and in Saccharomyces cerevisiae, using datasets of 445 and 170 affymetrix arrays, respectively. Using the area under the curve of the receiver operating characteristics and the F-measure as indicators, we showed the predictive performance of TNIFSED to be better than unsupervised state-of-the-art methods. TNIFSED performed slightly worse than the supervised SIRENE algorithm for the target genes identification of the TF having a wide range of yet identified target genes but better for TF having only few identified target genes. Our results indicate that TNIFSED is complementary to the SIRENE algorithm, and particularly suitable to discover target genes of "orphan" TFs.
Combination of a proteomics approach and reengineering of meso scale network models for prediction of mode-of-action for tyrosine kinase inhibitors.

PubMed

Balabanov, Stefan; Wilhelm, Thomas; Venz, Simone; Keller, Gunhild; Scharf, Christian; Pospisil, Heike; Braig, Melanie; Barett, Christine; Bokemeyer, Carsten; Walther, Reinhard; Brümmendorf, Tim H; Schuppert, Andreas

2013-01-01

In drug discovery, the characterisation of the precise modes of action (MoA) and of unwanted off-target effects of novel molecularly targeted compounds is of highest relevance. Recent approaches for identification of MoA have employed various techniques for modeling of well defined signaling pathways including structural information, changes in phenotypic behavior of cells and gene expression patterns after drug treatment. However, efficient approaches focusing on proteome wide data for the identification of MoA including interference with mutations are underrepresented. As mutations are key drivers of drug resistance in molecularly targeted tumor therapies, efficient analysis and modeling of downstream effects of mutations on drug MoA is a key to efficient development of improved targeted anti-cancer drugs. Here we present a combination of a global proteome analysis, reengineering of network models and integration of apoptosis data used to infer the mode-of-action of various tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) cell lines expressing wild type as well as TKI resistance conferring mutants of BCR-ABL. The inferred network models provide a tool to predict the main MoA of drugs as well as to grouping of drugs with known similar kinase inhibitory activity patterns in comparison to drugs with an additional MoA. We believe that our direct network reconstruction approach, demonstrated on proteomics data, can provide a complementary method to the established network reconstruction approaches for the preclinical modeling of the MoA of various types of targeted drugs in cancer treatment. Hence it may contribute to the more precise prediction of clinically relevant on- and off-target effects of TKIs.
Combination of a Proteomics Approach and Reengineering of Meso Scale Network Models for Prediction of Mode-of-Action for Tyrosine Kinase Inhibitors

PubMed Central

Balabanov, Stefan; Wilhelm, Thomas; Venz, Simone; Keller, Gunhild; Scharf, Christian; Pospisil, Heike; Braig, Melanie; Barett, Christine; Bokemeyer, Carsten; Walther, Reinhard

2013-01-01

In drug discovery, the characterisation of the precise modes of action (MoA) and of unwanted off-target effects of novel molecularly targeted compounds is of highest relevance. Recent approaches for identification of MoA have employed various techniques for modeling of well defined signaling pathways including structural information, changes in phenotypic behavior of cells and gene expression patterns after drug treatment. However, efficient approaches focusing on proteome wide data for the identification of MoA including interference with mutations are underrepresented. As mutations are key drivers of drug resistance in molecularly targeted tumor therapies, efficient analysis and modeling of downstream effects of mutations on drug MoA is a key to efficient development of improved targeted anti-cancer drugs. Here we present a combination of a global proteome analysis, reengineering of network models and integration of apoptosis data used to infer the mode-of-action of various tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) cell lines expressing wild type as well as TKI resistance conferring mutants of BCR-ABL. The inferred network models provide a tool to predict the main MoA of drugs as well as to grouping of drugs with known similar kinase inhibitory activity patterns in comparison to drugs with an additional MoA. We believe that our direct network reconstruction approach, demonstrated on proteomics data, can provide a complementary method to the established network reconstruction approaches for the preclinical modeling of the MoA of various types of targeted drugs in cancer treatment. Hence it may contribute to the more precise prediction of clinically relevant on- and off-target effects of TKIs. PMID:23326482
Reverse Engineering Cellular Networks with Information Theoretic Methods

PubMed Central

Villaverde, Alejandro F.; Ross, John; Banga, Julio R.

2013-01-01

Building mathematical models of cellular networks lies at the core of systems biology. It involves, among other tasks, the reconstruction of the structure of interactions between molecular components, which is known as network inference or reverse engineering. Information theory can help in the goal of extracting as much information as possible from the available data. A large number of methods founded on these concepts have been proposed in the literature, not only in biology journals, but in a wide range of areas. Their critical comparison is difficult due to the different focuses and the adoption of different terminologies. Here we attempt to review some of the existing information theoretic methodologies for network inference, and clarify their differences. While some of these methods have achieved notable success, many challenges remain, among which we can mention dealing with incomplete measurements, noisy data, counterintuitive behaviour emerging from nonlinear relations or feedback loops, and computational burden of dealing with large data sets. PMID:24709703
Macroscopic and microscopic spectral properties of brain networks during local and global synchronization

NASA Astrophysics Data System (ADS)

Maksimenko, Vladimir A.; Lüttjohann, Annika; Makarov, Vladimir V.; Goremyko, Mikhail V.; Koronovskii, Alexey A.; Nedaivozov, Vladimir; Runnova, Anastasia E.; van Luijtelaar, Gilles; Hramov, Alexander E.; Boccaletti, Stefano

2017-07-01

We introduce a practical and computationally not demanding technique for inferring interactions at various microscopic levels between the units of a network from the measurements and the processing of macroscopic signals. Starting from a network model of Kuramoto phase oscillators, which evolve adaptively according to homophilic and homeostatic adaptive principles, we give evidence that the increase of synchronization within groups of nodes (and the corresponding formation of synchronous clusters) causes also the defragmentation of the wavelet energy spectrum of the macroscopic signal. Our methodology is then applied to getting a glance into the microscopic interactions occurring in a neurophysiological system, namely, in the thalamocortical neural network of an epileptic brain of a rat, where the group electrical activity is registered by means of multichannel EEG. We demonstrate that it is possible to infer the degree of interaction between the interconnected regions of the brain during different types of brain activities and to estimate the regions' participation in the generation of the different levels of consciousness.
Circuit theory and model-based inference for landscape connectivity

USGS Publications Warehouse

Hanks, Ephraim M.; Hooten, Mevin B.

2013-01-01

Circuit theory has seen extensive recent use in the field of ecology, where it is often applied to study functional connectivity. The landscape is typically represented by a network of nodes and resistors, with the resistance between nodes a function of landscape characteristics. The effective distance between two locations on a landscape is represented by the resistance distance between the nodes in the network. Circuit theory has been applied to many other scientific fields for exploratory analyses, but parametric models for circuits are not common in the scientific literature. To model circuits explicitly, we demonstrate a link between Gaussian Markov random fields and contemporary circuit theory using a covariance structure that induces the necessary resistance distance. This provides a parametric model for second-order observations from such a system. In the landscape ecology setting, the proposed model provides a simple framework where inference can be obtained for effects that landscape features have on functional connectivity. We illustrate the approach through a landscape genetics study linking gene flow in alpine chamois (Rupicapra rupicapra) to the underlying landscape.
Intelligent control for modeling of real-time reservoir operation, part II: artificial neural network with operating rule curves

NASA Astrophysics Data System (ADS)

Chang, Ya-Ting; Chang, Li-Chiu; Chang, Fi-John

2005-04-01

To bridge the gap between academic research and actual operation, we propose an intelligent control system for reservoir operation. The methodology includes two major processes, the knowledge acquired and implemented, and the inference system. In this study, a genetic algorithm (GA) and a fuzzy rule base (FRB) are used to extract knowledge based on the historical inflow data with a design objective function and on the operating rule curves respectively. The adaptive network-based fuzzy inference system (ANFIS) is then used to implement the knowledge, to create the fuzzy inference system, and then to estimate the optimal reservoir operation. To investigate its applicability and practicability, the Shihmen reservoir, Taiwan, is used as a case study. For the purpose of comparison, a simulation of the currently used M-5 operating rule curve is also performed. The results demonstrate that (1) the GA is an efficient way to search the optimal input-output patterns, (2) the FRB can extract the knowledge from the operating rule curves, and (3) the ANFIS models built on different types of knowledge can produce much better performance than the traditional M-5 curves in real-time reservoir operation. Moreover, we show that the model can be more intelligent for reservoir operation if more information (or knowledge) is involved.
Leveraging Structural Characteristics of Interdependent Networks to Model Non-linear Cascading Characteristics

DTIC Science & Technology

2015-06-29

17.476 237.18 17.5 237.2 91.64216359 6.752418 -20- References Asuncion, A., Welling, M., Smyth, P., & Teh , P. Y. ( 2009 ). On Smoothing and inference...networks of interdependent programs [Lewin 1999, Flowe et al., 2009 ]. Also, the acquisition paradigm established in statute 10 U.S.C. 2434, policy...results. Number of topics (k) for input data: Quality of results of modeling can be measured using a factor called perplexity (Asuncion et al. 2009
Generating probabilistic Boolean networks from a prescribed transition probability matrix.

PubMed

Ching, W-K; Chen, X; Tsing, N-K

2009-11-01

Probabilistic Boolean networks (PBNs) have received much attention in modeling genetic regulatory networks. A PBN can be regarded as a Markov chain process and is characterised by a transition probability matrix. In this study, the authors propose efficient algorithms for constructing a PBN when its transition probability matrix is given. The complexities of the algorithms are also analysed. This is an interesting inverse problem in network inference using steady-state data. The problem is important as most microarray data sets are assumed to be obtained from sampling the steady-state.
From Coexpression to Coregulation: An Approach to Inferring Transcriptional Regulation Among Gene Classes from Large-Scale Expression Data

NASA Technical Reports Server (NTRS)

Mjolsness, Eric; Castano, Rebecca; Mann, Tobias; Wold, Barbara

2000-01-01

We provide preliminary evidence that existing algorithms for inferring small-scale gene regulation networks from gene expression data can be adapted to large-scale gene expression data coming from hybridization microarrays. The essential steps are (I) clustering many genes by their expression time-course data into a minimal set of clusters of co-expressed genes, (2) theoretically modeling the various conditions under which the time-courses are measured using a continuous-time analog recurrent neural network for the cluster mean time-courses, (3) fitting such a regulatory model to the cluster mean time courses by simulated annealing with weight decay, and (4) analysing several such fits for commonalities in the circuit parameter sets including the connection matrices. This procedure can be used to assess the adequacy of existing and future gene expression time-course data sets for determining transcriptional regulatory relationships such as coregulation.
Statistical modelling of networked human-automation performance using working memory capacity.

PubMed

Ahmed, Nisar; de Visser, Ewart; Shaw, Tyler; Mohamed-Ameen, Amira; Campbell, Mark; Parasuraman, Raja

2014-01-01

This study examines the challenging problem of modelling the interaction between individual attentional limitations and decision-making performance in networked human-automation system tasks. Analysis of real experimental data from a task involving networked supervision of multiple unmanned aerial vehicles by human participants shows that both task load and network message quality affect performance, but that these effects are modulated by individual differences in working memory (WM) capacity. These insights were used to assess three statistical approaches for modelling and making predictions with real experimental networked supervisory performance data: classical linear regression, non-parametric Gaussian processes and probabilistic Bayesian networks. It is shown that each of these approaches can help designers of networked human-automated systems cope with various uncertainties in order to accommodate future users by linking expected operating conditions and performance from real experimental data to observable cognitive traits like WM capacity. Practitioner Summary: Working memory (WM) capacity helps account for inter-individual variability in operator performance in networked unmanned aerial vehicle supervisory tasks. This is useful for reliable performance prediction near experimental conditions via linear models; robust statistical prediction beyond experimental conditions via Gaussian process models and probabilistic inference about unknown task conditions/WM capacities via Bayesian network models.

Drug-disease association and drug-repositioning predictions in complex diseases using causal inference-probabilistic matrix factorization.

PubMed

Yang, Jihong; Li, Zheng; Fan, Xiaohui; Cheng, Yiyu

2014-09-22

The high incidence of complex diseases has become a worldwide threat to human health. Multiple targets and pathways are perturbed during the pathological process of complex diseases. Systematic investigation of complex relationship between drugs and diseases is necessary for new association discovery and drug repurposing. For this purpose, three causal networks were constructed herein for cardiovascular diseases, diabetes mellitus, and neoplasms, respectively. A causal inference-probabilistic matrix factorization (CI-PMF) approach was proposed to predict and classify drug-disease associations, and further used for drug-repositioning predictions. First, multilevel systematic relations between drugs and diseases were integrated from heterogeneous databases to construct causal networks connecting drug-target-pathway-gene-disease. Then, the association scores between drugs and diseases were assessed by evaluating a drug's effects on multiple targets and pathways. Furthermore, PMF models were learned based on known interactions, and associations were then classified into three types by trained models. Finally, therapeutic associations were predicted based upon the ranking of association scores and predicted association types. In terms of drug-disease association prediction, modified causal inference included in CI-PMF outperformed existing causal inference with a higher AUC (area under receiver operating characteristic curve) score and greater precision. Moreover, CI-PMF performed better than single modified causal inference in predicting therapeutic drug-disease associations. In the top 30% of predicted associations, 58.6% (136/232), 50.8% (31/61), and 39.8% (140/352) hit known therapeutic associations, while precisions obtained by the latter were only 10.2% (231/2264), 8.8% (36/411), and 9.7% (189/1948). Clinical verifications were further conducted for the top 100 newly predicted therapeutic associations. As a result, 21, 12, and 32 associations have been studied and many treatment effects of drugs on diseases were investigated for cardiovascular diseases, diabetes mellitus, and neoplasms, respectively. Related chains in causal networks were extracted for these 65 clinical-verified associations, and we further illustrated the therapeutic role of etodolac in breast cancer by inferred chains. Overall, CI-PMF is a useful approach for associating drugs with complex diseases and provides potential values for drug repositioning.
Visual recognition and inference using dynamic overcomplete sparse learning.

PubMed

Murray, Joseph F; Kreutz-Delgado, Kenneth

2007-09-01

We present a hierarchical architecture and learning algorithm for visual recognition and other visual inference tasks such as imagination, reconstruction of occluded images, and expectation-driven segmentation. Using properties of biological vision for guidance, we posit a stochastic generative world model and from it develop a simplified world model (SWM) based on a tractable variational approximation that is designed to enforce sparse coding. Recent developments in computational methods for learning overcomplete representations (Lewicki & Sejnowski, 2000; Teh, Welling, Osindero, & Hinton, 2003) suggest that overcompleteness can be useful for visual tasks, and we use an overcomplete dictionary learning algorithm (Kreutz-Delgado, et al., 2003) as a preprocessing stage to produce accurate, sparse codings of images. Inference is performed by constructing a dynamic multilayer network with feedforward, feedback, and lateral connections, which is trained to approximate the SWM. Learning is done with a variant of the back-propagation-through-time algorithm, which encourages convergence to desired states within a fixed number of iterations. Vision tasks require large networks, and to make learning efficient, we take advantage of the sparsity of each layer to update only a small subset of elements in a large weight matrix at each iteration. Experiments on a set of rotated objects demonstrate various types of visual inference and show that increasing the degree of overcompleteness improves recognition performance in difficult scenes with occluded objects in clutter.
IMNN: Information Maximizing Neural Networks

NASA Astrophysics Data System (ADS)

Charnock, Tom; Lavaux, Guilhem; Wandelt, Benjamin D.

2018-04-01

This software trains artificial neural networks to find non-linear functionals of data that maximize Fisher information: information maximizing neural networks (IMNNs). As compressing large data sets vastly simplifies both frequentist and Bayesian inference, important information may be inadvertently missed. Likelihood-free inference based on automatically derived IMNN summaries produces summaries that are good approximations to sufficient statistics. IMNNs are robustly capable of automatically finding optimal, non-linear summaries of the data even in cases where linear compression fails: inferring the variance of Gaussian signal in the presence of noise, inferring cosmological parameters from mock simulations of the Lyman-α forest in quasar spectra, and inferring frequency-domain parameters from LISA-like detections of gravitational waveforms. In this final case, the IMNN summary outperforms linear data compression by avoiding the introduction of spurious likelihood maxima.
A null model for Pearson coexpression networks.

PubMed

Gobbi, Andrea; Jurman, Giuseppe

2015-01-01

Gene coexpression networks inferred by correlation from high-throughput profiling such as microarray data represent simple but effective structures for discovering and interpreting linear gene relationships. In recent years, several approaches have been proposed to tackle the problem of deciding when the resulting correlation values are statistically significant. This is most crucial when the number of samples is small, yielding a non-negligible chance that even high correlation values are due to random effects. Here we introduce a novel hard thresholding solution based on the assumption that a coexpression network inferred by randomly generated data is expected to be empty. The threshold is theoretically derived by means of an analytic approach and, as a deterministic independent null model, it depends only on the dimensions of the starting data matrix, with assumptions on the skewness of the data distribution compatible with the structure of gene expression levels data. We show, on synthetic and array datasets, that the proposed threshold is effective in eliminating all false positive links, with an offsetting cost in terms of false negative detected edges.
Differentiable cortical networks for inferences concerning people's intentions versus physical causality.

PubMed

Mason, Robert A; Just, Marcel Adam

2011-02-01

Cortical activity associated with generating an inference was measured using fMRI. Participants read three-sentence passages that differed in whether or not an inference needed to be drawn to understand them. The inference was based on either a protagonist's intention or a physical consequence of a character's action. Activation was expected in Theory of Mind brain regions for the passages based on protagonists' intentions but not for the physical consequence passages. The activation measured in the right temporo-parietal junction was greater in the intentional passages than in the consequence passages, consistent with predictions from a Theory of Mind perspective. In contrast, there was increased occipital activation in the physical inference passages. For both types of passage, the cortical activity related to the reading of the critical inference sentence demonstrated a recruitment of a common inference cortical network. This general inference-related activation appeared bilaterally in the language processing areas (the inferior frontal gyrus, the temporal gyrus, and the angular gyrus), as well as in the medial to superior frontal gyrus, which has been found to be active in Theory of Mind tasks. These findings are consistent with the hypothesis that component areas of the discourse processing network are recruited as needed based on the nature of the inference. A Protagonist monitoring and synthesis network is proposed as a more accurate account for Theory of Mind activation during narrative comprehension. Copyright © 2010 Wiley-Liss, Inc.
Bayesian Networks for Modeling Dredging Decisions

DTIC Science & Technology

2011-10-01

change scenarios. Arctic Expert elicitation Netica Bacon et al . 2002 Identify factors that might lead to a change in land use from farming to...tree) algorithms developed by Lauritzen and Spiegelhalter (1988) and Jensen et al . (1990). Statistical inference is simply the process of...causality when constructing a Bayesian network (Kjaerulff and Madsen 2008, Darwiche 2009, Marcot et al . 2006). A knowledge representation approach is the
Nonparametric Representations for Integrated Inference, Control, and Sensing

DTIC Science & Technology

2015-10-01

Learning (ICML), 2013. [20] Jeff Donahue, Yangqing Jia, Oriol Vinyals, Judy Hoffman, Ning Zhang, Eric Tzeng, and Trevor Darrell. DeCAF: A deep ...unlimited. Multi-layer feature learning “SuperVision” Convolutional Neural Network (CNN) ImageNet Classification with Deep Convolutional Neural Networks...to develop a new framework for autonomous operations that will extend the state of the art in distributed learning and modeling from data, and
Displayed Trees Do Not Determine Distinguishability Under the Network Multispecies Coalescent

PubMed Central

Zhu, Sha; Degnan, James H.

2017-01-01

Abstract Recent work in estimating species relationships from gene trees has included inferring networks assuming that past hybridization has occurred between species. Probabilistic models using the multispecies coalescent can be used in this framework for likelihood-based inference of both network topologies and parameters, including branch lengths and hybridization parameters. A difficulty for such methods is that it is not always clear whether, or to what extent, networks are identifiable—that is whether there could be two distinct networks that lead to the same distribution of gene trees. For cases in which incomplete lineage sorting occurs in addition to hybridization, we demonstrate a new representation of the species network likelihood that expresses the probability distribution of the gene tree topologies as a linear combination of gene tree distributions given a set of species trees. This representation makes it clear that in some cases in which two distinct networks give the same distribution of gene trees when sampling one allele per species, the two networks can be distinguished theoretically when multiple individuals are sampled per species. This result means that network identifiability is not only a function of the trees displayed by the networks but also depends on allele sampling within species. We additionally give an example in which two networks that display exactly the same trees can be distinguished from their gene trees even when there is only one lineage sampled per species. PMID:27780899
NIMEFI: gene regulatory network inference using multiple ensemble feature importance algorithms.

PubMed

Ruyssinck, Joeri; Huynh-Thu, Vân Anh; Geurts, Pierre; Dhaene, Tom; Demeester, Piet; Saeys, Yvan

2014-01-01

One of the long-standing open challenges in computational systems biology is the topology inference of gene regulatory networks from high-throughput omics data. Recently, two community-wide efforts, DREAM4 and DREAM5, have been established to benchmark network inference techniques using gene expression measurements. In these challenges the overall top performer was the GENIE3 algorithm. This method decomposes the network inference task into separate regression problems for each gene in the network in which the expression values of a particular target gene are predicted using all other genes as possible predictors. Next, using tree-based ensemble methods, an importance measure for each predictor gene is calculated with respect to the target gene and a high feature importance is considered as putative evidence of a regulatory link existing between both genes. The contribution of this work is twofold. First, we generalize the regression decomposition strategy of GENIE3 to other feature importance methods. We compare the performance of support vector regression, the elastic net, random forest regression, symbolic regression and their ensemble variants in this setting to the original GENIE3 algorithm. To create the ensemble variants, we propose a subsampling approach which allows us to cast any feature selection algorithm that produces a feature ranking into an ensemble feature importance algorithm. We demonstrate that the ensemble setting is key to the network inference task, as only ensemble variants achieve top performance. As second contribution, we explore the effect of using rankwise averaged predictions of multiple ensemble algorithms as opposed to only one. We name this approach NIMEFI (Network Inference using Multiple Ensemble Feature Importance algorithms) and show that this approach outperforms all individual methods in general, although on a specific network a single method can perform better. An implementation of NIMEFI has been made publicly available.
Inferring protein domains associated with drug side effects based on drug-target interaction network

PubMed Central

2013-01-01

Background Most phenotypic effects of drugs are involved in the interactions between drugs and their target proteins, however, our knowledge about the molecular mechanism of the drug-target interactions is very limited. One of challenging issues in recent pharmaceutical science is to identify the underlying molecular features which govern drug-target interactions. Results In this paper, we make a systematic analysis of the correlation between drug side effects and protein domains, which we call "pharmacogenomic features," based on the drug-target interaction network. We detect drug side effects and protein domains that appear jointly in known drug-target interactions, which is made possible by using classifiers with sparse models. It is shown that the inferred pharmacogenomic features can be used for predicting potential drug-target interactions. We also discuss advantages and limitations of the pharmacogenomic features, compared with the chemogenomic features that are the associations between drug chemical substructures and protein domains. Conclusion The inferred side effect-domain association network is expected to be useful for estimating common drug side effects for different protein families and characteristic drug side effects for specific protein domains. PMID:24565527
Quantum Inference on Bayesian Networks

NASA Astrophysics Data System (ADS)

Yoder, Theodore; Low, Guang Hao; Chuang, Isaac

2014-03-01

Because quantum physics is naturally probabilistic, it seems reasonable to expect physical systems to describe probabilities and their evolution in a natural fashion. Here, we use quantum computation to speedup sampling from a graphical probability model, the Bayesian network. A specialization of this sampling problem is approximate Bayesian inference, where the distribution on query variables is sampled given the values e of evidence variables. Inference is a key part of modern machine learning and artificial intelligence tasks, but is known to be NP-hard. Classically, a single unbiased sample is obtained from a Bayesian network on n variables with at most m parents per node in time (nmP(e) - 1 / 2) , depending critically on P(e) , the probability the evidence might occur in the first place. However, by implementing a quantum version of rejection sampling, we obtain a square-root speedup, taking (n2m P(e) -1/2) time per sample. The speedup is the result of amplitude amplification, which is proving to be broadly applicable in sampling and machine learning tasks. In particular, we provide an explicit and efficient circuit construction that implements the algorithm without the need for oracle access.
An Intuitive Dashboard for Bayesian Network Inference

NASA Astrophysics Data System (ADS)

Reddy, Vikas; Charisse Farr, Anna; Wu, Paul; Mengersen, Kerrie; Yarlagadda, Prasad K. D. V.

2014-03-01

Current Bayesian network software packages provide good graphical interface for users who design and develop Bayesian networks for various applications. However, the intended end-users of these networks may not necessarily find such an interface appealing and at times it could be overwhelming, particularly when the number of nodes in the network is large. To circumvent this problem, this paper presents an intuitive dashboard, which provides an additional layer of abstraction, enabling the end-users to easily perform inferences over the Bayesian networks. Unlike most software packages, which display the nodes and arcs of the network, the developed tool organises the nodes based on the cause-and-effect relationship, making the user-interaction more intuitive and friendly. In addition to performing various types of inferences, the users can conveniently use the tool to verify the behaviour of the developed Bayesian network. The tool has been developed using QT and SMILE libraries in C++.
A Survey of Statistical Models for Reverse Engineering Gene Regulatory Networks

PubMed Central

Huang, Yufei; Tienda-Luna, Isabel M.; Wang, Yufeng

2009-01-01

Statistical models for reverse engineering gene regulatory networks are surveyed in this article. To provide readers with a system-level view of the modeling issues in this research, a graphical modeling framework is proposed. This framework serves as the scaffolding on which the review of different models can be systematically assembled. Based on the framework, we review many existing models for many aspects of gene regulation; the pros and cons of each model are discussed. In addition, network inference algorithms are also surveyed under the graphical modeling framework by the categories of point solutions and probabilistic solutions and the connections and differences among the algorithms are provided. This survey has the potential to elucidate the development and future of reverse engineering GRNs and bring statistical signal processing closer to the core of this research. PMID:20046885
Neural model of gene regulatory network: a survey on supportive meta-heuristics.

PubMed

Biswas, Surama; Acharyya, Sriyankar

2016-06-01

Gene regulatory network (GRN) is produced as a result of regulatory interactions between different genes through their coded proteins in cellular context. Having immense importance in disease detection and drug finding, GRN has been modelled through various mathematical and computational schemes and reported in survey articles. Neural and neuro-fuzzy models have been the focus of attraction in bioinformatics. Predominant use of meta-heuristic algorithms in training neural models has proved its excellence. Considering these facts, this paper is organized to survey neural modelling schemes of GRN and the efficacy of meta-heuristic algorithms towards parameter learning (i.e. weighting connections) within the model. This survey paper renders two different structure-related approaches to infer GRN which are global structure approach and substructure approach. It also describes two neural modelling schemes, such as artificial neural network/recurrent neural network based modelling and neuro-fuzzy modelling. The meta-heuristic algorithms applied so far to learn the structure and parameters of neutrally modelled GRN have been reviewed here.
Co-Inheritance Analysis within the Domains of Life Substantially Improves Network Inference by Phylogenetic Profiling

PubMed Central

Shin, Junha; Lee, Insuk

2015-01-01

Phylogenetic profiling, a network inference method based on gene inheritance profiles, has been widely used to construct functional gene networks in microbes. However, its utility for network inference in higher eukaryotes has been limited. An improved algorithm with an in-depth understanding of pathway evolution may overcome this limitation. In this study, we investigated the effects of taxonomic structures on co-inheritance analysis using 2,144 reference species in four query species: Escherichia coli, Saccharomyces cerevisiae, Arabidopsis thaliana, and Homo sapiens. We observed three clusters of reference species based on a principal component analysis of the phylogenetic profiles, which correspond to the three domains of life—Archaea, Bacteria, and Eukaryota—suggesting that pathways inherit primarily within specific domains or lower-ranked taxonomic groups during speciation. Hence, the co-inheritance pattern within a taxonomic group may be eroded by confounding inheritance patterns from irrelevant taxonomic groups. We demonstrated that co-inheritance analysis within domains substantially improved network inference not only in microbe species but also in the higher eukaryotes, including humans. Although we observed two sub-domain clusters of reference species within Eukaryota, co-inheritance analysis within these sub-domain taxonomic groups only marginally improved network inference. Therefore, we conclude that co-inheritance analysis within domains is the optimal approach to network inference with the given reference species. The construction of a series of human gene networks with increasing sample sizes of the reference species for each domain revealed that the size of the high-accuracy networks increased as additional reference species genomes were included, suggesting that within-domain co-inheritance analysis will continue to expand human gene networks as genomes of additional species are sequenced. Taken together, we propose that co-inheritance analysis within the domains of life will greatly potentiate the use of the expected onslaught of sequenced genomes in the study of molecular pathways in higher eukaryotes. PMID:26394049
Screening Models of Aquifer Heterogeneity Using the Flow Dimension

NASA Astrophysics Data System (ADS)

Walker, D. D.; Cello, P. A.; Roberts, R. M.; Valocchi, A. J.

2007-12-01

Despite advances in test interpretation and modeling, typical groundwater modeling studies only indirectly use the parameters and information inferred from hydraulic tests. In particular, the Generalized Radial Flow approach to test interpretation infers the flow dimension, a parameter describing the geometry of the flow field during a hydraulic test. Noninteger values of the flow dimension often are inferred for tests in highly heterogeneous aquifers, yet subsequent modeling studies typically ignore the flow dimension. Monte Carlo analyses of detailed numerical models of aquifer tests examine the flow dimension for several stochastic models of heterogeneous transmissivity, T(x). These include multivariate lognormal, fractional Brownian motion, a site percolation network, and discrete linear features with lengths distributed as power-law. The behavior of the simulated flow dimensions are compared to the flow dimensions observed for multiple aquifer tests in a fractured dolomite aquifer in the Great Lakes region of North America. The combination of multiple hydraulic tests, observed fracture patterns, and the Monte Carlo results are used to screen models of heterogeneity and their parameters for subsequent groundwater flow modeling.
Porcine Tissue-Specific Regulatory Networks Derived from Meta-Analysis of the Transcriptome

PubMed Central

Pérez-Montarelo, Dafne; Hudson, Nicholas J.; Fernández, Ana I.; Ramayo-Caldas, Yuliaxis; Dalrymple, Brian P.; Reverter, Antonio

2012-01-01

The processes that drive tissue identity and differentiation remain unclear for most tissue types. So are the gene networks and transcription factors (TF) responsible for the differential structure and function of each particular tissue, and this is particularly true for non model species with incomplete genomic resources. To better understand the regulation of genes responsible for tissue identity in pigs, we have inferred regulatory networks from a meta-analysis of 20 gene expression studies spanning 480 Porcine Affymetrix chips for 134 experimental conditions on 27 distinct tissues. We developed a mixed-model normalization approach with a covariance structure that accommodated the disparity in the origin of the individual studies, and obtained the normalized expression of 12,320 genes across the 27 tissues. Using this resource, we constructed a network, based on the co-expression patterns of 1,072 TF and 1,232 tissue specific genes. The resulting network is consistent with the known biology of tissue development. Within the network, genes clustered by tissue and tissues clustered by site of embryonic origin. These clusters were significantly enriched for genes annotated in key relevant biological processes and confirm gene functions and interactions from the literature. We implemented a Regulatory Impact Factor (RIF) metric to identify the key regulators in skeletal muscle and tissues from the central nervous systems. The normalization of the meta-analysis, the inference of the gene co-expression network and the RIF metric, operated synergistically towards a successful search for tissue-specific regulators. Novel among these findings are evidence suggesting a novel key role of ERCC3 as a muscle regulator. Together, our results recapitulate the known biology behind tissue specificity and provide new valuable insights in a less studied but valuable model species. PMID:23049964
Bayesian networks improve causal environmental ...

EPA Pesticide Factsheets

Rule-based weight of evidence approaches to ecological risk assessment may not account for uncertainties and generally lack probabilistic integration of lines of evidence. Bayesian networks allow causal inferences to be made from evidence by including causal knowledge about the problem, using this knowledge with probabilistic calculus to combine multiple lines of evidence, and minimizing biases in predicting or diagnosing causal relationships. Too often, sources of uncertainty in conventional weight of evidence approaches are ignored that can be accounted for with Bayesian networks. Specifying and propagating uncertainties improve the ability of models to incorporate strength of the evidence in the risk management phase of an assessment. Probabilistic inference from a Bayesian network allows evaluation of changes in uncertainty for variables from the evidence. The network structure and probabilistic framework of a Bayesian approach provide advantages over qualitative approaches in weight of evidence for capturing the impacts of multiple sources of quantifiable uncertainty on predictions of ecological risk. Bayesian networks can facilitate the development of evidence-based policy under conditions of uncertainty by incorporating analytical inaccuracies or the implications of imperfect information, structuring and communicating causal issues through qualitative directed graph formulations, and quantitatively comparing the causal power of multiple stressors on value
Integration of Steady-State and Temporal Gene Expression Data for the Inference of Gene Regulatory Networks

PubMed Central

Wang, Yi Kan; Hurley, Daniel G.; Schnell, Santiago; Print, Cristin G.; Crampin, Edmund J.

2013-01-01

We develop a new regression algorithm, cMIKANA, for inference of gene regulatory networks from combinations of steady-state and time-series gene expression data. Using simulated gene expression datasets to assess the accuracy of reconstructing gene regulatory networks, we show that steady-state and time-series data sets can successfully be combined to identify gene regulatory interactions using the new algorithm. Inferring gene networks from combined data sets was found to be advantageous when using noisy measurements collected with either lower sampling rates or a limited number of experimental replicates. We illustrate our method by applying it to a microarray gene expression dataset from human umbilical vein endothelial cells (HUVECs) which combines time series data from treatment with growth factor TNF and steady state data from siRNA knockdown treatments. Our results suggest that the combination of steady-state and time-series datasets may provide better prediction of RNA-to-RNA interactions, and may also reveal biological features that cannot be identified from dynamic or steady state information alone. Finally, we consider the experimental design of genomics experiments for gene regulatory network inference and show that network inference can be improved by incorporating steady-state measurements with time-series data. PMID:23967277
Inferring tectonic activity using drainage network and RT model: an example from the western Himalayas, India

NASA Astrophysics Data System (ADS)

Sahoo, Ramendra; Jain, Vikrant

2017-04-01

Morphology of the landscape and derived features are regarded to be an important tool for inferring about tectonic activity in an area, since surface exposures of these subsurface processes may not be available or may get eroded away over time. This has led to an extensive research in application of the non-planar morphological attributes like river long profile and hypsometry for tectonic studies, whereas drainage network as a proxy for tectonic activity has not been explored greatly. Though, significant work has been done on drainage network pattern which started in a qualitative manner and over the years, has evolved to incorporate more quantitative aspects, like studying the evolution of a network under the influence of external and internal controls. Random Topology (RT) model is one of these concepts, which elucidates the connection between evolution of a drainage network pattern and the entropy of the drainage system and it states that in absence of any geological controls, a natural population of channel networks will be topologically random. We have used the entropy maximization principle to provide a theoretical structure for the RT model. Furthermore, analysis was carried out on the drainage network structures around Jwalamukhi thrust in the Kangra reentrant in western Himalayas, India, to investigate the tectonic activity in the region. Around one thousand networks were extracted from the foot-wall (fw) and hanging-wall (hw) region of the thrust sheet and later categorized based on their magnitudes. We have adopted the goodness of fit test for comparing the network patterns in fw and hw drainage with those derived using the RT model. The null hypothesis for the test was, the drainage networks in the fw are statistically more similar than those on the hw, to the network patterns derived using the RT model for any given magnitude. The test results are favorable to our null hypothesis for networks with smaller magnitudes (< 9), whereas for larger magnitudes, both hw and fw networks were found to be statistically not similar to the model network patterns. Calculation of pattern frequency for each magnitude and subsequent hypothesis testing were carried out using Matlab (v R2015a). Our results will help to define drainage network pattern as one of the geomorphic proxy to identify tectonically active area. This study also serve as a supplementary proof of the neo-tectonic control on the morphology of landscape and its derivatives around the Jwalamukhi thrust. Additionally, it will help to verify the theory of probabilistic evolution of drainage networks.

Qualitative reasoning for biological network inference from systematic perturbation experiments.

PubMed

Badaloni, Silvana; Di Camillo, Barbara; Sambo, Francesco

2012-01-01

The systematic perturbation of the components of a biological system has been proven among the most informative experimental setups for the identification of causal relations between the components. In this paper, we present Systematic Perturbation-Qualitative Reasoning (SPQR), a novel Qualitative Reasoning approach to automate the interpretation of the results of systematic perturbation experiments. Our method is based on a qualitative abstraction of the experimental data: for each perturbation experiment, measured values of the observed variables are modeled as lower, equal or higher than the measurements in the wild type condition, when no perturbation is applied. The algorithm exploits a set of IF-THEN rules to infer causal relations between the variables, analyzing the patterns of propagation of the perturbation signals through the biological network, and is specifically designed to minimize the rate of false positives among the inferred relations. Tested on both simulated and real perturbation data, SPQR indeed exhibits a significantly higher precision than the state of the art.
Perceptual learning as improved probabilistic inference in early sensory areas.

PubMed

Bejjanki, Vikranth R; Beck, Jeffrey M; Lu, Zhong-Lin; Pouget, Alexandre

2011-05-01

Extensive training on simple tasks such as fine orientation discrimination results in large improvements in performance, a form of learning known as perceptual learning. Previous models have argued that perceptual learning is due to either sharpening and amplification of tuning curves in early visual areas or to improved probabilistic inference in later visual areas (at the decision stage). However, early theories are inconsistent with the conclusions of psychophysical experiments manipulating external noise, whereas late theories cannot explain the changes in neural responses that have been reported in cortical areas V1 and V4. Here we show that we can capture both the neurophysiological and behavioral aspects of perceptual learning by altering only the feedforward connectivity in a recurrent network of spiking neurons so as to improve probabilistic inference in early visual areas. The resulting network shows modest changes in tuning curves, in line with neurophysiological reports, along with a marked reduction in the amplitude of pairwise noise correlations.
Measuring Learning Progressions Using Bayesian Modeling in Complex Assessments

ERIC Educational Resources Information Center

Rutstein, Daisy Wise

2012-01-01

This research examines issues regarding model estimation and robustness in the use of Bayesian Inference Networks (BINs) for measuring Learning Progressions (LPs). It provides background information on LPs and how they might be used in practice. Two simulation studies are performed, along with real data examples. The first study examines the case…
Identification of coal seam strata from geophysical logs of borehole using Adaptive Neuro-Fuzzy Inference System

NASA Astrophysics Data System (ADS)

Yegireddi, Satyanarayana; Uday Bhaskar, G.

2009-01-01

Different parameters obtained through well-logging geophysical sensors such as SP, resistivity, gamma-gamma, neutron, natural gamma and acoustic, help in identification of strata and estimation of the physical, electrical and acoustical properties of the subsurface lithology. Strong and conspicuous changes in some of the log parameters associated with any particular stratigraphy formation, are function of its composition, physical properties and help in classification. However some substrata show moderate values in respective log parameters and make difficult to identify or assess the type of strata, if we go by the standard variability ranges of any log parameters and visual inspection. The complexity increases further with more number of sensors involved. An attempt is made to identify the type of stratigraphy from borehole geophysical log data using a combined approach of neural networks and fuzzy logic, known as Adaptive Neuro-Fuzzy Inference System. A model is built based on a few data sets (geophysical logs) of known stratigraphy of in coal areas of Kothagudem, Godavari basin and further the network model is used as test model to infer the lithology of a borehole from their geophysical logs, not used in simulation. The results are very encouraging and the model is able to decipher even thin cola seams and other strata from borehole geophysical logs. The model can be further modified to assess the physical properties of the strata, if the corresponding ground truth is made available for simulation.
Autonomous mental development with selective attention, object perception, and knowledge representation

NASA Astrophysics Data System (ADS)

Ban, Sang-Woo; Lee, Minho

2008-04-01

Knowledge-based clustering and autonomous mental development remains a high priority research topic, among which the learning techniques of neural networks are used to achieve optimal performance. In this paper, we present a new framework that can automatically generate a relevance map from sensory data that can represent knowledge regarding objects and infer new knowledge about novel objects. The proposed model is based on understating of the visual what pathway in our brain. A stereo saliency map model can selectively decide salient object areas by additionally considering local symmetry feature. The incremental object perception model makes clusters for the construction of an ontology map in the color and form domains in order to perceive an arbitrary object, which is implemented by the growing fuzzy topology adaptive resonant theory (GFTART) network. Log-polar transformed color and form features for a selected object are used as inputs of the GFTART. The clustered information is relevant to describe specific objects, and the proposed model can automatically infer an unknown object by using the learned information. Experimental results with real data have demonstrated the validity of this approach.
Modification of Hazen's equation in coarse grained soils by soft computing techniques

NASA Astrophysics Data System (ADS)

Kaynar, Oguz; Yilmaz, Isik; Marschalko, Marian; Bednarik, Martin; Fojtova, Lucie

2013-04-01

Hazen first proposed a Relationship between coefficient of permeability (k) and effective grain size (d10) was first proposed by Hazen, and it was then extended by some other researchers. However many attempts were done for estimation of k, correlation coefficients (R2) of the models were generally lower than ~0.80 and whole grain size distribution curves were not included in the assessments. Soft computing techniques such as; artificial neural networks, fuzzy inference systems, genetic algorithms, etc. and their hybrids are now being successfully used as an alternative tool. In this study, use of some soft computing techniques such as Artificial Neural Networks (ANNs) (MLP, RBF, etc.) and Adaptive Neuro-Fuzzy Inference System (ANFIS) for prediction of permeability of coarse grained soils was described, and Hazen's equation was then modificated. It was found that the soft computing models exhibited high performance in prediction of permeability coefficient. However four different kinds of ANN algorithms showed similar prediction performance, results of MLP was found to be relatively more accurate than RBF models. The most reliable prediction was obtained from ANFIS model.
Effects of phase vector and history extension on prediction power of adaptive-network based fuzzy inference system (ANFIS) model for a real scale anaerobic wastewater treatment plant operating under unsteady state.

PubMed

Perendeci, Altinay; Arslan, Sever; Tanyolaç, Abdurrahman; Celebi, Serdar S

2009-10-01

A conceptual neural fuzzy model based on adaptive-network based fuzzy inference system, ANFIS, was proposed using available input on-line and off-line operational variables for a sugar factory anaerobic wastewater treatment plant operating under unsteady state to estimate the effluent chemical oxygen demand, COD. The predictive power of the developed model was improved as a new approach by adding the phase vector and the recent values of COD up to 5-10 days, longer than overall retention time of wastewater in the system. History of last 10 days for COD effluent with two-valued phase vector in the input variable matrix including all parameters had more predictive power. History of 7 days with two-valued phase vector in the matrix comprised of only on-line variables yielded fairly well estimations. The developed ANFIS model with phase vector and history extension has been able to adequately represent the behavior of the treatment system.
NetBenchmark: a bioconductor package for reproducible benchmarks of gene regulatory network inference.

PubMed

Bellot, Pau; Olsen, Catharina; Salembier, Philippe; Oliveras-Vergés, Albert; Meyer, Patrick E

2015-09-29

In the last decade, a great number of methods for reconstructing gene regulatory networks from expression data have been proposed. However, very few tools and datasets allow to evaluate accurately and reproducibly those methods. Hence, we propose here a new tool, able to perform a systematic, yet fully reproducible, evaluation of transcriptional network inference methods. Our open-source and freely available Bioconductor package aggregates a large set of tools to assess the robustness of network inference algorithms against different simulators, topologies, sample sizes and noise intensities. The benchmarking framework that uses various datasets highlights the specialization of some methods toward network types and data. As a result, it is possible to identify the techniques that have broad overall performances.
Ontology Mapping Neural Network: An Approach to Learning and Inferring Correspondences among Ontologies

ERIC Educational Resources Information Center

Peng, Yefei

2010-01-01

An ontology mapping neural network (OMNN) is proposed in order to learn and infer correspondences among ontologies. It extends the Identical Elements Neural Network (IENN)'s ability to represent and map complex relationships. The learning dynamics of simultaneous (interlaced) training of similar tasks interact at the shared connections of the…
Inference of cancer-specific gene regulatory networks using soft computing rules.

PubMed

Wang, Xiaosheng; Gotoh, Osamu

2010-03-24

Perturbations of gene regulatory networks are essentially responsible for oncogenesis. Therefore, inferring the gene regulatory networks is a key step to overcoming cancer. In this work, we propose a method for inferring directed gene regulatory networks based on soft computing rules, which can identify important cause-effect regulatory relations of gene expression. First, we identify important genes associated with a specific cancer (colon cancer) using a supervised learning approach. Next, we reconstruct the gene regulatory networks by inferring the regulatory relations among the identified genes, and their regulated relations by other genes within the genome. We obtain two meaningful findings. One is that upregulated genes are regulated by more genes than downregulated ones, while downregulated genes regulate more genes than upregulated ones. The other one is that tumor suppressors suppress tumor activators and activate other tumor suppressors strongly, while tumor activators activate other tumor activators and suppress tumor suppressors weakly, indicating the robustness of biological systems. These findings provide valuable insights into the pathogenesis of cancer.
Generative models for network neuroscience: prospects and promise

PubMed Central

Betzel, Richard F.

2017-01-01

Network neuroscience is the emerging discipline concerned with investigating the complex patterns of interconnections found in neural systems, and identifying principles with which to understand them. Within this discipline, one particularly powerful approach is network generative modelling, in which wiring rules are algorithmically implemented to produce synthetic network architectures with the same properties as observed in empirical network data. Successful models can highlight the principles by which a network is organized and potentially uncover the mechanisms by which it grows and develops. Here, we review the prospects and promise of generative models for network neuroscience. We begin with a primer on network generative models, with a discussion of compressibility and predictability, and utility in intuiting mechanisms, followed by a short history on their use in network science, broadly. We then discuss generative models in practice and application, paying particular attention to the critical need for cross-validation. Next, we review generative models of biological neural networks, both at the cellular and large-scale level, and across a variety of species including Caenorhabditis elegans, Drosophila, mouse, rat, cat, macaque and human. We offer a careful treatment of a few relevant distinctions, including differences between generative models and null models, sufficiency and redundancy, inferring and claiming mechanism, and functional and structural connectivity. We close with a discussion of future directions, outlining exciting frontiers both in empirical data collection efforts as well as in method and theory development that, together, further the utility of the generative network modelling approach for network neuroscience. PMID:29187640
Relationships between probabilistic Boolean networks and dynamic Bayesian networks as models of gene regulatory networks

PubMed Central

Lähdesmäki, Harri; Hautaniemi, Sampsa; Shmulevich, Ilya; Yli-Harja, Olli

2006-01-01

A significant amount of attention has recently been focused on modeling of gene regulatory networks. Two frequently used large-scale modeling frameworks are Bayesian networks (BNs) and Boolean networks, the latter one being a special case of its recent stochastic extension, probabilistic Boolean networks (PBNs). PBN is a promising model class that generalizes the standard rule-based interactions of Boolean networks into the stochastic setting. Dynamic Bayesian networks (DBNs) is a general and versatile model class that is able to represent complex temporal stochastic processes and has also been proposed as a model for gene regulatory systems. In this paper, we concentrate on these two model classes and demonstrate that PBNs and a certain subclass of DBNs can represent the same joint probability distribution over their common variables. The major benefit of introducing the relationships between the models is that it opens up the possibility of applying the standard tools of DBNs to PBNs and vice versa. Hence, the standard learning tools of DBNs can be applied in the context of PBNs, and the inference methods give a natural way of handling the missing values in PBNs which are often present in gene expression measurements. Conversely, the tools for controlling the stationary behavior of the networks, tools for projecting networks onto sub-networks, and efficient learning schemes can be used for DBNs. In other words, the introduced relationships between the models extend the collection of analysis tools for both model classes. PMID:17415411
Robust Inference of Genetic Exchange Communities from Microbial Genomes Using TF-IDF

PubMed Central

Cong, Yingnan; Chan, Yao-ban; Phillips, Charles A.; Langston, Michael A.; Ragan, Mark A.

2017-01-01

Bacteria and archaea can exchange genetic material across lineages through processes of lateral genetic transfer (LGT). Collectively, these exchange relationships can be modeled as a network and analyzed using concepts from graph theory. In particular, densely connected regions within an LGT network have been defined as genetic exchange communities (GECs). However, it has been problematic to construct networks in which edges solely represent LGT. Here we apply term frequency-inverse document frequency (TF-IDF), an alignment-free method originating from document analysis, to infer regions of lateral origin in bacterial genomes. We examine four empirical datasets of different size (number of genomes) and phyletic breadth, varying a key parameter (word length k) within bounds established in previous work. We map the inferred lateral regions to genes in recipient genomes, and construct networks in which the nodes are groups of genomes, and the edges natively represent LGT. We then extract maximum and maximal cliques (i.e., GECs) from these graphs, and identify nodes that belong to GECs across a wide range of k. Most surviving lateral transfer has happened within these GECs. Using Gene Ontology enrichment tests we demonstrate that biological processes associated with metabolism, regulation and transport are often over-represented among the genes affected by LGT within these communities. These enrichments are largely robust to change of k. PMID:28154557
Evolution of the social network of scientific collaborations

NASA Astrophysics Data System (ADS)

Barabasi, Albert-Laszlo; Jeong, Hawoong; Neda, Zoltan; Ravasz, Erzsebet; Schubert, Andras; Vicsek, Tamas

2002-03-01

The co-authorship network of scientists represents a prototype of complex evolving networks. By mapping the electronic database containing all relevant journals in mathematics and neuro-science for an eight-year period (1991-98), we infer the dynamic and the structural mechanisms that govern the evolution and topology of this complex system. First, empirical measurements allow us to uncover the topological measures that characterize the network at a given moment, as well as the time evolution of these quantities. The results indicate that the network is scale-free, and that the network evolution is governed by preferential attachment, affecting both internal and external links. However, in contrast with most model predictions the average degree increases in time, and the node separation decreases. Second, we propose a simple model that captures the network's time evolution. Third, numerical simulations are used to uncover the behavior of quantities that could not be predicted analytically.
Proteomic Screening and Lasso Regression Reveal Differential Signaling in Insulin and Insulin-like Growth Factor I (IGF1) Pathways.

PubMed

Erdem, Cemal; Nagle, Alison M; Casa, Angelo J; Litzenburger, Beate C; Wang, Yu-Fen; Taylor, D Lansing; Lee, Adrian V; Lezon, Timothy R

2016-09-01

Insulin and insulin-like growth factor I (IGF1) influence cancer risk and progression through poorly understood mechanisms. To better understand the roles of insulin and IGF1 signaling in breast cancer, we combined proteomic screening with computational network inference to uncover differences in IGF1 and insulin induced signaling. Using reverse phase protein array, we measured the levels of 134 proteins in 21 breast cancer cell lines stimulated with IGF1 or insulin for up to 48 h. We then constructed directed protein expression networks using three separate methods: (i) lasso regression, (ii) conventional matrix inversion, and (iii) entropy maximization. These networks, named here as the time translation models, were analyzed and the inferred interactions were ranked by differential magnitude to identify pathway differences. The two top candidates, chosen for experimental validation, were shown to regulate IGF1/insulin induced phosphorylation events. First, acetyl-CoA carboxylase (ACC) knock-down was shown to increase the level of mitogen-activated protein kinase (MAPK) phosphorylation. Second, stable knock-down of E-Cadherin increased the phospho-Akt protein levels. Both of the knock-down perturbations incurred phosphorylation responses stronger in IGF1 stimulated cells compared with insulin. Overall, the time-translation modeling coupled to wet-lab experiments has proven to be powerful in inferring differential interactions downstream of IGF1 and insulin signaling, in vitro. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
Gene network analysis: from heart development to cardiac therapy.

PubMed

Ferrazzi, Fulvia; Bellazzi, Riccardo; Engel, Felix B

2015-03-01

Networks offer a flexible framework to represent and analyse the complex interactions between components of cellular systems. In particular gene networks inferred from expression data can support the identification of novel hypotheses on regulatory processes. In this review we focus on the use of gene network analysis in the study of heart development. Understanding heart development will promote the elucidation of the aetiology of congenital heart disease and thus possibly improve diagnostics. Moreover, it will help to establish cardiac therapies. For example, understanding cardiac differentiation during development will help to guide stem cell differentiation required for cardiac tissue engineering or to enhance endogenous repair mechanisms. We introduce different methodological frameworks to infer networks from expression data such as Boolean and Bayesian networks. Then we present currently available temporal expression data in heart development and discuss the use of network-based approaches in published studies. Collectively, our literature-based analysis indicates that gene network analysis constitutes a promising opportunity to infer therapy-relevant regulatory processes in heart development. However, the use of network-based approaches has so far been limited by the small amount of samples in available datasets. Thus, we propose to acquire high-resolution temporal expression data to improve the mathematical descriptions of regulatory processes obtained with gene network inference methodologies. Especially probabilistic methods that accommodate the intrinsic variability of biological systems have the potential to contribute to a deeper understanding of heart development.
Choosing experiments to accelerate collective discovery

PubMed Central

Rzhetsky, Andrey; Foster, Jacob G.; Foster, Ian T.

2015-01-01

A scientist’s choice of research problem affects his or her personal career trajectory. Scientists’ combined choices affect the direction and efficiency of scientific discovery as a whole. In this paper, we infer preferences that shape problem selection from patterns of published findings and then quantify their efficiency. We represent research problems as links between scientific entities in a knowledge network. We then build a generative model of discovery informed by qualitative research on scientific problem selection. We map salient features from this literature to key network properties: an entity’s importance corresponds to its degree centrality, and a problem’s difficulty corresponds to the network distance it spans. Drawing on millions of papers and patents published over 30 years, we use this model to infer the typical research strategy used to explore chemical relationships in biomedicine. This strategy generates conservative research choices focused on building up knowledge around important molecules. These choices become more conservative over time. The observed strategy is efficient for initial exploration of the network and supports scientific careers that require steady output, but is inefficient for science as a whole. Through supercomputer experiments on a sample of the network, we study thousands of alternatives and identify strategies much more efficient at exploring mature knowledge networks. We find that increased risk-taking and the publication of experimental failures would substantially improve the speed of discovery. We consider institutional shifts in grant making, evaluation, and publication that would help realize these efficiencies. PMID:26554009
Gene network biological validity based on gene-gene interaction relevance.

PubMed

Gómez-Vela, Francisco; Díaz-Díaz, Norberto

2014-01-01

In recent years, gene networks have become one of the most useful tools for modeling biological processes. Many inference gene network algorithms have been developed as techniques for extracting knowledge from gene expression data. Ensuring the reliability of the inferred gene relationships is a crucial task in any study in order to prove that the algorithms used are precise. Usually, this validation process can be carried out using prior biological knowledge. The metabolic pathways stored in KEGG are one of the most widely used knowledgeable sources for analyzing relationships between genes. This paper introduces a new methodology, GeneNetVal, to assess the biological validity of gene networks based on the relevance of the gene-gene interactions stored in KEGG metabolic pathways. Hence, a complete KEGG pathway conversion into a gene association network and a new matching distance based on gene-gene interaction relevance are proposed. The performance of GeneNetVal was established with three different experiments. Firstly, our proposal is tested in a comparative ROC analysis. Secondly, a randomness study is presented to show the behavior of GeneNetVal when the noise is increased in the input network. Finally, the ability of GeneNetVal to detect biological functionality of the network is shown.
Erosion and refilling of the plasmasphere during a geomagnetic storm modeled by a neural network

NASA Astrophysics Data System (ADS)

Chu, X. N.; Bortnik, J.; Li, W.; Ma, Q.; Angelopoulos, V.; Thorne, R. M.

2017-07-01

We present a history-dependent model of the equatorial plasma density of the inner magnetosphere using a feedforward neural network with two hidden layers. As the model inputs, we take locations and time series of SYM-H, AL, and F10.7 indices. By considering not only the instantaneous values but also the past values of geomagnetic and solar indices, the model is history dependent on levels of geomagnetic and solar activity. The modeled electron density is continuous both spatially and temporally so that the evolution of the density can be studied (such as plasmaspheric refilling). The model is trained using the electron density inferred from the spacecraft potential from three THEMIS probes. The equatorial electron density is shown to be accurately reconstructed with a correlation coefficient of r 0.953 between data and model target. Since the model is history dependent, it succeeds in reconstructing various density features and dynamic behaviors, such as the quiet time plasmasphere, erosion and recovery of the plasmasphere, as well as the plume formation during a storm on 4 February 2011. Our model may provide unprecedented insight into the behavior of the equatorial density at any time and location; as an example we show the inferred refilling rate from our model and compare it to previous estimates.
Community-Reviewed Biological Network Models for Toxicology and Drug Discovery Applications

PubMed Central

Namasivayam, Aishwarya Alex; Morales, Alejandro Ferreiro; Lacave, Ángela María Fajardo; Tallam, Aravind; Simovic, Borislav; Alfaro, David Garrido; Bobbili, Dheeraj Reddy; Martin, Florian; Androsova, Ganna; Shvydchenko, Irina; Park, Jennifer; Calvo, Jorge Val; Hoeng, Julia; Peitsch, Manuel C.; Racero, Manuel González Vélez; Biryukov, Maria; Talikka, Marja; Pérez, Modesto Berraquero; Rohatgi, Neha; Díaz-Díaz, Noberto; Mandarapu, Rajesh; Ruiz, Rubén Amián; Davidyan, Sergey; Narayanasamy, Shaman; Boué, Stéphanie; Guryanova, Svetlana; Arbas, Susana Martínez; Menon, Swapna; Xiang, Yang

2016-01-01

Biological network models offer a framework for understanding disease by describing the relationships between the mechanisms involved in the regulation of biological processes. Crowdsourcing can efficiently gather feedback from a wide audience with varying expertise. In the Network Verification Challenge, scientists verified and enhanced a set of 46 biological networks relevant to lung and chronic obstructive pulmonary disease. The networks were built using Biological Expression Language and contain detailed information for each node and edge, including supporting evidence from the literature. Network scoring of public transcriptomics data inferred perturbation of a subset of mechanisms and networks that matched the measured outcomes. These results, based on a computable network approach, can be used to identify novel mechanisms activated in disease, quantitatively compare different treatments and time points, and allow for assessment of data with low signal. These networks are periodically verified by the crowd to maintain an up-to-date suite of networks for toxicology and drug discovery applications. PMID:27429547

Predicting wettability behavior of fluorosilica coated metal surface using optimum neural network

NASA Astrophysics Data System (ADS)

Taghipour-Gorjikolaie, Mehran; Valipour Motlagh, Naser

2018-02-01

The interaction between variables, which are effective on the surface wettability, is very complex to predict the contact angles and sliding angles of liquid drops. In this paper, in order to solve this complexity, artificial neural network was used to develop reliable models for predicting the angles of liquid drops. Experimental data are divided into training data and testing data. By using training data and feed forward structure for the neural network and using particle swarm optimization for training the neural network based models, the optimum models were developed. The obtained results showed that regression index for the proposed models for the contact angles and sliding angles are 0.9874 and 0.9920, respectively. As it can be seen, these values are close to unit and it means the reliable performance of the models. Also, it can be inferred from the results that the proposed model have more reliable performance than multi-layer perceptron and radial basis function based models.
Recent development and biomedical applications of probabilistic Boolean networks

PubMed Central

2013-01-01

Probabilistic Boolean network (PBN) modelling is a semi-quantitative approach widely used for the study of the topology and dynamic aspects of biological systems. The combined use of rule-based representation and probability makes PBN appealing for large-scale modelling of biological networks where degrees of uncertainty need to be considered. A considerable expansion of our knowledge in the field of theoretical research on PBN can be observed over the past few years, with a focus on network inference, network intervention and control. With respect to areas of applications, PBN is mainly used for the study of gene regulatory networks though with an increasing emergence in signal transduction, metabolic, and also physiological networks. At the same time, a number of computational tools, facilitating the modelling and analysis of PBNs, are continuously developed. A concise yet comprehensive review of the state-of-the-art on PBN modelling is offered in this article, including a comparative discussion on PBN versus similar models with respect to concepts and biomedical applications. Due to their many advantages, we consider PBN to stand as a suitable modelling framework for the description and analysis of complex biological systems, ranging from molecular to physiological levels. PMID:23815817
Network inference from functional experimental data (Conference Presentation)

NASA Astrophysics Data System (ADS)

Desrosiers, Patrick; Labrecque, Simon; Tremblay, Maxime; Bélanger, Mathieu; De Dorlodot, Bertrand; Côté, Daniel C.

2016-03-01

Functional connectivity maps of neuronal networks are critical tools to understand how neurons form circuits, how information is encoded and processed by neurons, how memory is shaped, and how these basic processes are altered under pathological conditions. Current light microscopy allows to observe calcium or electrical activity of thousands of neurons simultaneously, yet assessing comprehensive connectivity maps directly from such data remains a non-trivial analytical task. There exist simple statistical methods, such as cross-correlation and Granger causality, but they only detect linear interactions between neurons. Other more involved inference methods inspired by information theory, such as mutual information and transfer entropy, identify more accurately connections between neurons but also require more computational resources. We carried out a comparative study of common connectivity inference methods. The relative accuracy and computational cost of each method was determined via simulated fluorescence traces generated with realistic computational models of interacting neurons in networks of different topologies (clustered or non-clustered) and sizes (10-1000 neurons). To bridge the computational and experimental works, we observed the intracellular calcium activity of live hippocampal neuronal cultures infected with the fluorescent calcium marker GCaMP6f. The spontaneous activity of the networks, consisting of 50-100 neurons per field of view, was recorded from 20 to 50 Hz on a microscope controlled by a homemade software. We implemented all connectivity inference methods in the software, which rapidly loads calcium fluorescence movies, segments the images, extracts the fluorescence traces, and assesses the functional connections (with strengths and directions) between each pair of neurons. We used this software to assess, in real time, the functional connectivity from real calcium imaging data in basal conditions, under plasticity protocols, and epileptic conditions.
Inferring gene and protein interactions using PubMed citations and consensus Bayesian networks.

PubMed

Deeter, Anthony; Dalman, Mark; Haddad, Joseph; Duan, Zhong-Hui

2017-01-01

The PubMed database offers an extensive set of publication data that can be useful, yet inherently complex to use without automated computational techniques. Data repositories such as the Genomic Data Commons (GDC) and the Gene Expression Omnibus (GEO) offer experimental data storage and retrieval as well as curated gene expression profiles. Genetic interaction databases, including Reactome and Ingenuity Pathway Analysis, offer pathway and experiment data analysis using data curated from these publications and data repositories. We have created a method to generate and analyze consensus networks, inferring potential gene interactions, using large numbers of Bayesian networks generated by data mining publications in the PubMed database. Through the concept of network resolution, these consensus networks can be tailored to represent possible genetic interactions. We designed a set of experiments to confirm that our method is stable across variation in both sample and topological input sizes. Using gene product interactions from the KEGG pathway database and data mining PubMed publication abstracts, we verify that regardless of the network resolution or the inferred consensus network, our method is capable of inferring meaningful gene interactions through consensus Bayesian network generation with multiple, randomized topological orderings. Our method can not only confirm the existence of currently accepted interactions, but has the potential to hypothesize new ones as well. We show our method confirms the existence of known gene interactions such as JAK-STAT-PI3K-AKT-mTOR, infers novel gene interactions such as RAS- Bcl-2 and RAS-AKT, and found significant pathway-pathway interactions between the JAK-STAT signaling and Cardiac Muscle Contraction KEGG pathways.
[Spectral quantitative analysis by nonlinear partial least squares based on neural network internal model for flue gas of thermal power plant].

PubMed

Cao, Hui; Li, Yao-Jiang; Zhou, Yan; Wang, Yan-Xia

2014-11-01

To deal with nonlinear characteristics of spectra data for the thermal power plant flue, a nonlinear partial least square (PLS) analysis method with internal model based on neural network is adopted in the paper. The latent variables of the independent variables and the dependent variables are extracted by PLS regression firstly, and then they are used as the inputs and outputs of neural network respectively to build the nonlinear internal model by train process. For spectra data of flue gases of the thermal power plant, PLS, the nonlinear PLS with the internal model of back propagation neural network (BP-NPLS), the non-linear PLS with the internal model of radial basis function neural network (RBF-NPLS) and the nonlinear PLS with the internal model of adaptive fuzzy inference system (ANFIS-NPLS) are compared. The root mean square error of prediction (RMSEP) of sulfur dioxide of BP-NPLS, RBF-NPLS and ANFIS-NPLS are reduced by 16.96%, 16.60% and 19.55% than that of PLS, respectively. The RMSEP of nitric oxide of BP-NPLS, RBF-NPLS and ANFIS-NPLS are reduced by 8.60%, 8.47% and 10.09% than that of PLS, respectively. The RMSEP of nitrogen dioxide of BP-NPLS, RBF-NPLS and ANFIS-NPLS are reduced by 2.11%, 3.91% and 3.97% than that of PLS, respectively. Experimental results show that the nonlinear PLS is more suitable for the quantitative analysis of glue gas than PLS. Moreover, by using neural network function which can realize high approximation of nonlinear characteristics, the nonlinear partial least squares method with internal model mentioned in this paper have well predictive capabilities and robustness, and could deal with the limitations of nonlinear partial least squares method with other internal model such as polynomial and spline functions themselves under a certain extent. ANFIS-NPLS has the best performance with the internal model of adaptive fuzzy inference system having ability to learn more and reduce the residuals effectively. Hence, ANFIS-NPLS is an accurate and useful quantitative thermal power plant flue gas analysis method.
The use of large scale datasets for understanding traffic network state.

DOT National Transportation Integrated Search

2013-09-01

The goal of this proposal is to develop novel modeling techniques to infer individual activity patterns from the large scale cell phone : datasets and taxi data from NYC. As such this research offers a paradigm shift from traditional transportation m...
Ability of the current global observing network to constrain N2O sources and sinks

NASA Astrophysics Data System (ADS)

Millet, D. B.; Wells, K. C.; Chaliyakunnel, S.; Griffis, T. J.; Henze, D. K.; Bousserez, N.

2014-12-01

The global observing network for atmospheric N2O combines flask and in-situ measurements at ground stations with sustained and campaign-based aircraft observations. In this talk we apply a new global model of N2O (based on GEOS-Chem) and its adjoint to assess the strengths and weaknesses of this network for quantifying N2O emissions. We employ an ensemble of pseudo-observation analyses to evaluate the relative constraints provided by ground-based (surface, tall tower) and airborne (HIPPO, CARIBIC) observations, and the extent to which variability (e.g. associated with pulsing or seasonality of emissions) not captured by the a priori inventory can bias the inferred fluxes. We find that the ground-based and HIPPO datasets each provide a stronger constraint on the distribution of global emissions than does the CARIBIC dataset on its own. Given appropriate initial conditions, we find that our inferred surface fluxes are insensitive to model errors in the stratospheric loss rate of N2O over the timescale of our analysis (2 years); however, the same is not necessarily true for model errors in stratosphere-troposphere exchange. Finally, we examine the a posteriori error reduction distribution to identify priority locations for future N2O measurements.
A Topological Criterion for Filtering Information in Complex Brain Networks

PubMed Central

Latora, Vito; Chavez, Mario

2017-01-01

In many biological systems, the network of interactions between the elements can only be inferred from experimental measurements. In neuroscience, non-invasive imaging tools are extensively used to derive either structural or functional brain networks in-vivo. As a result of the inference process, we obtain a matrix of values corresponding to a fully connected and weighted network. To turn this into a useful sparse network, thresholding is typically adopted to cancel a percentage of the weakest connections. The structural properties of the resulting network depend on how much of the inferred connectivity is eventually retained. However, how to objectively fix this threshold is still an open issue. We introduce a criterion, the efficiency cost optimization (ECO), to select a threshold based on the optimization of the trade-off between the efficiency of a network and its wiring cost. We prove analytically and we confirm through numerical simulations that the connection density maximizing this trade-off emphasizes the intrinsic properties of a given network, while preserving its sparsity. Moreover, this density threshold can be determined a-priori, since the number of connections to filter only depends on the network size according to a power-law. We validate this result on several brain networks, from micro- to macro-scales, obtained with different imaging modalities. Finally, we test the potential of ECO in discriminating brain states with respect to alternative filtering methods. ECO advances our ability to analyze and compare biological networks, inferred from experimental data, in a fast and principled way. PMID:28076353
A continuous optimization approach for inferring parameters in mathematical models of regulatory networks.

PubMed

Deng, Zhimin; Tian, Tianhai

2014-07-29

The advances of systems biology have raised a large number of sophisticated mathematical models for describing the dynamic property of complex biological systems. One of the major steps in developing mathematical models is to estimate unknown parameters of the model based on experimentally measured quantities. However, experimental conditions limit the amount of data that is available for mathematical modelling. The number of unknown parameters in mathematical models may be larger than the number of observation data. The imbalance between the number of experimental data and number of unknown parameters makes reverse-engineering problems particularly challenging. To address the issue of inadequate experimental data, we propose a continuous optimization approach for making reliable inference of model parameters. This approach first uses a spline interpolation to generate continuous functions of system dynamics as well as the first and second order derivatives of continuous functions. The expanded dataset is the basis to infer unknown model parameters using various continuous optimization criteria, including the error of simulation only, error of both simulation and the first derivative, or error of simulation as well as the first and second derivatives. We use three case studies to demonstrate the accuracy and reliability of the proposed new approach. Compared with the corresponding discrete criteria using experimental data at the measurement time points only, numerical results of the ERK kinase activation module show that the continuous absolute-error criteria using both function and high order derivatives generate estimates with better accuracy. This result is also supported by the second and third case studies for the G1/S transition network and the MAP kinase pathway, respectively. This suggests that the continuous absolute-error criteria lead to more accurate estimates than the corresponding discrete criteria. We also study the robustness property of these three models to examine the reliability of estimates. Simulation results show that the models with estimated parameters using continuous fitness functions have better robustness properties than those using the corresponding discrete fitness functions. The inference studies and robustness analysis suggest that the proposed continuous optimization criteria are effective and robust for estimating unknown parameters in mathematical models.
Macrocell path loss prediction using artificial intelligence techniques

NASA Astrophysics Data System (ADS)

Usman, Abraham U.; Okereke, Okpo U.; Omizegba, Elijah E.

2014-04-01

The prediction of propagation loss is a practical non-linear function approximation problem which linear regression or auto-regression models are limited in their ability to handle. However, some computational Intelligence techniques such as artificial neural networks (ANNs) and adaptive neuro-fuzzy inference systems (ANFISs) have been shown to have great ability to handle non-linear function approximation and prediction problems. In this study, the multiple layer perceptron neural network (MLP-NN), radial basis function neural network (RBF-NN) and an ANFIS network were trained using actual signal strength measurement taken at certain suburban areas of Bauchi metropolis, Nigeria. The trained networks were then used to predict propagation losses at the stated areas under differing conditions. The predictions were compared with the prediction accuracy of the popular Hata model. It was observed that ANFIS model gave a better fit in all cases having higher R2 values in each case and on average is more robust than MLP and RBF models as it generalises better to a different data.
Evolving RBF neural networks for adaptive soft-sensor design.

PubMed

Alexandridis, Alex

2013-12-01

This work presents an adaptive framework for building soft-sensors based on radial basis function (RBF) neural network models. The adaptive fuzzy means algorithm is utilized in order to evolve an RBF network, which approximates the unknown system based on input-output data from it. The methodology gradually builds the RBF network model, based on two separate levels of adaptation: On the first level, the structure of the hidden layer is modified by adding or deleting RBF centers, while on the second level, the synaptic weights are adjusted with the recursive least squares with exponential forgetting algorithm. The proposed approach is tested on two different systems, namely a simulated nonlinear DC Motor and a real industrial reactor. The results show that the produced soft-sensors can be successfully applied to model the two nonlinear systems. A comparison with two different adaptive modeling techniques, namely a dynamic evolving neural-fuzzy inference system (DENFIS) and neural networks trained with online backpropagation, highlights the advantages of the proposed methodology.
A Corrected Formulation of the Multilayer Model (MLM) for Inferring Gaseous Dry Deposition to Vegetated Surfaces

NASA Technical Reports Server (NTRS)

Saylor, Rick D.; Wolfe, Glenn M.; Meyers, Tilden P.; Hicks, Bruce B.

2014-01-01

The Multilayer Model (MLM) has been used for many years to infer dry deposition fluxes from measured trace species concentrations and standard meteorological measurements for national networks in the U.S., including the U.S. Environmental Protection Agency's Clean Air Status and Trends Network (CASTNet). MLM utilizes a resistance analogy to calculate deposition velocities appropriate for whole vegetative canopies, while employing a multilayer integration to account for vertically varying meteorology, canopy morphology and radiative transfer within the canopy. However, the MLM formulation, as it was originally presented and as it has been subsequently employed, contains a non-physical representation related to the leaf-level quasi-laminar boundary layer resistance that affects the calculation of the total canopy resistance. In this note, the non-physical representation of the canopy resistance as originally formulated in MLM is discussed and a revised, physically consistent, formulation is suggested as a replacement. The revised canopy resistance formulation reduces estimates of HNO3 deposition velocities by as much as 38% during mid-day as compared to values generated by the original formulation. Inferred deposition velocities for SO2 and O3 are not significantly altered by the change in formulation (less than 3%). Inferred deposition loadings of oxidized and total nitrogen from CASTNet data may be reduced by 10-20% and 5-10%, respectively, for the Eastern U. S. when employing the revised formulation of MLM as compared to the original formulation.
Distributed micro-releases of bioterror pathogens : threat characterizations and epidemiology from uncertain patient observables.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wolf, Michael M.; Marzouk, Youssef M.; Adams, Brian M.

2008-10-01

Terrorist attacks using an aerosolized pathogen preparation have gained credibility as a national security concern since the anthrax attacks of 2001. The ability to characterize the parameters of such attacks, i.e., to estimate the number of people infected, the time of infection, the average dose received, and the rate of disease spread in contemporary American society (for contagious diseases), is important when planning a medical response. For non-contagious diseases, we address the characterization problem by formulating a Bayesian inverse problem predicated on a short time-series of diagnosed patients exhibiting symptoms. To keep the approach relevant for response planning, we limitmore » ourselves to 3.5 days of data. In computational tests performed for anthrax, we usually find these observation windows sufficient, especially if the outbreak model employed in the inverse problem is accurate. For contagious diseases, we formulated a Bayesian inversion technique to infer both pathogenic transmissibility and the social network from outbreak observations, ensuring that the two determinants of spreading are identified separately. We tested this technique on data collected from a 1967 smallpox epidemic in Abakaliki, Nigeria. We inferred, probabilistically, different transmissibilities in the structured Abakaliki population, the social network, and the chain of transmission. Finally, we developed an individual-based epidemic model to realistically simulate the spread of a rare (or eradicated) disease in a modern society. This model incorporates the mixing patterns observed in an (American) urban setting and accepts, as model input, pathogenic transmissibilities estimated from historical outbreaks that may have occurred in socio-economic environments with little resemblance to contemporary society. Techniques were also developed to simulate disease spread on static and sampled network reductions of the dynamic social networks originally in the individual-based model, yielding faster, though approximate, network-based epidemic models. These reduced-order models are useful in scenario analysis for medical response planning, as well as in computationally intensive inverse problems.« less
Cytoscape: a software environment for integrated models of biomolecular interaction networks.

PubMed

Shannon, Paul; Markiel, Andrew; Ozier, Owen; Baliga, Nitin S; Wang, Jonathan T; Ramage, Daniel; Amin, Nada; Schwikowski, Benno; Ideker, Trey

2003-11-01

Cytoscape is an open source software project for integrating biomolecular interaction networks with high-throughput expression data and other molecular states into a unified conceptual framework. Although applicable to any system of molecular components and interactions, Cytoscape is most powerful when used in conjunction with large databases of protein-protein, protein-DNA, and genetic interactions that are increasingly available for humans and model organisms. Cytoscape's software Core provides basic functionality to layout and query the network; to visually integrate the network with expression profiles, phenotypes, and other molecular states; and to link the network to databases of functional annotations. The Core is extensible through a straightforward plug-in architecture, allowing rapid development of additional computational analyses and features. Several case studies of Cytoscape plug-ins are surveyed, including a search for interaction pathways correlating with changes in gene expression, a study of protein complexes involved in cellular recovery to DNA damage, inference of a combined physical/functional interaction network for Halobacterium, and an interface to detailed stochastic/kinetic gene regulatory models.
Nonlinear dynamics of ice-wedge networks and resulting sensitivity to severe cooling events.

PubMed

Plug, L J; Werner, B T

2002-06-27

Patterns of subsurface wedges of ice that form along cooling-induced tension fractures, expressed at the ground surface by ridges or troughs spaced 10 30 m apart, are ubiquitous in polar lowlands. Fossilized ice wedges, which are widespread at lower latitudes, have been used to infer the duration and mean temperature of cold periods within Proterozoic and Quaternary climates, and recent climate trends have been inferred from fracture frequency in active ice wedges. Here we present simulations from a numerical model for the evolution of ice-wedge networks over a range of climate scenarios, based on the interactions between thermal tensile stress, fracture and ice wedges. We find that short-lived periods of severe cooling permanently alter the spacing between ice wedges as well as their fracture frequency. This affects the rate at which the widths of ice wedges increase as well as the network's response to subsequent climate change. We conclude that wedge spacing and width in ice-wedge networks mainly reflect infrequent episodes of rapidly falling ground temperatures rather than mean conditions.
Image feature based GPS trace filtering for road network generation and road segmentation

DOE PAGES

Yuan, Jiangye; Cheriyadat, Anil M.

2015-10-19

We propose a new method to infer road networks from GPS trace data and accurately segment road regions in high-resolution aerial images. Unlike previous efforts that rely on GPS traces alone, we exploit image features to infer road networks from noisy trace data. The inferred road network is used to guide road segmentation. We show that the number of image segments spanned by the traces and the trace orientation validated with image features are important attributes for identifying GPS traces on road regions. Based on filtered traces , we construct road networks and integrate them with image features to segmentmore » road regions. Lastly, our experiments show that the proposed method produces more accurate road networks than the leading method that uses GPS traces alone, and also achieves high accuracy in segmenting road regions even with very noisy GPS data.« less
Image feature based GPS trace filtering for road network generation and road segmentation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yuan, Jiangye; Cheriyadat, Anil M.

We propose a new method to infer road networks from GPS trace data and accurately segment road regions in high-resolution aerial images. Unlike previous efforts that rely on GPS traces alone, we exploit image features to infer road networks from noisy trace data. The inferred road network is used to guide road segmentation. We show that the number of image segments spanned by the traces and the trace orientation validated with image features are important attributes for identifying GPS traces on road regions. Based on filtered traces , we construct road networks and integrate them with image features to segmentmore » road regions. Lastly, our experiments show that the proposed method produces more accurate road networks than the leading method that uses GPS traces alone, and also achieves high accuracy in segmenting road regions even with very noisy GPS data.« less
NIMEFI: Gene Regulatory Network Inference using Multiple Ensemble Feature Importance Algorithms

PubMed Central

Ruyssinck, Joeri; Huynh-Thu, Vân Anh; Geurts, Pierre; Dhaene, Tom; Demeester, Piet; Saeys, Yvan

2014-01-01

One of the long-standing open challenges in computational systems biology is the topology inference of gene regulatory networks from high-throughput omics data. Recently, two community-wide efforts, DREAM4 and DREAM5, have been established to benchmark network inference techniques using gene expression measurements. In these challenges the overall top performer was the GENIE3 algorithm. This method decomposes the network inference task into separate regression problems for each gene in the network in which the expression values of a particular target gene are predicted using all other genes as possible predictors. Next, using tree-based ensemble methods, an importance measure for each predictor gene is calculated with respect to the target gene and a high feature importance is considered as putative evidence of a regulatory link existing between both genes. The contribution of this work is twofold. First, we generalize the regression decomposition strategy of GENIE3 to other feature importance methods. We compare the performance of support vector regression, the elastic net, random forest regression, symbolic regression and their ensemble variants in this setting to the original GENIE3 algorithm. To create the ensemble variants, we propose a subsampling approach which allows us to cast any feature selection algorithm that produces a feature ranking into an ensemble feature importance algorithm. We demonstrate that the ensemble setting is key to the network inference task, as only ensemble variants achieve top performance. As second contribution, we explore the effect of using rankwise averaged predictions of multiple ensemble algorithms as opposed to only one. We name this approach NIMEFI (Network Inference using Multiple Ensemble Feature Importance algorithms) and show that this approach outperforms all individual methods in general, although on a specific network a single method can perform better. An implementation of NIMEFI has been made publicly available. PMID:24667482
A symmetric multivariate leakage correction for MEG connectomes

PubMed Central

Colclough, G.L.; Brookes, M.J.; Smith, S.M.; Woolrich, M.W.

2015-01-01

Ambiguities in the source reconstruction of magnetoencephalographic (MEG) measurements can cause spurious correlations between estimated source time-courses. In this paper, we propose a symmetric orthogonalisation method to correct for these artificial correlations between a set of multiple regions of interest (ROIs). This process enables the straightforward application of network modelling methods, including partial correlation or multivariate autoregressive modelling, to infer connectomes, or functional networks, from the corrected ROIs. Here, we apply the correction to simulated MEG recordings of simple networks and to a resting-state dataset collected from eight subjects, before computing the partial correlations between power envelopes of the corrected ROItime-courses. We show accurate reconstruction of our simulated networks, and in the analysis of real MEGresting-state connectivity, we find dense bilateral connections within the motor and visual networks, together with longer-range direct fronto-parietal connections. PMID:25862259
Bankruptcy prediction based on financial ratios using Jordan Recurrent Neural Networks: a case study in Polish companies

NASA Astrophysics Data System (ADS)

Hardinata, Lingga; Warsito, Budi; Suparti

2018-05-01

Complexity of bankruptcy causes the accurate models of bankruptcy prediction difficult to be achieved. Various prediction models have been developed to improve the accuracy of bankruptcy predictions. Machine learning has been widely used to predict because of its adaptive capabilities. Artificial Neural Networks (ANN) is one of machine learning which proved able to complete inference tasks such as prediction and classification especially in data mining. In this paper, we propose the implementation of Jordan Recurrent Neural Networks (JRNN) to classify and predict corporate bankruptcy based on financial ratios. Feedback interconnection in JRNN enable to make the network keep important information well allowing the network to work more effectively. The result analysis showed that JRNN works very well in bankruptcy prediction with average success rate of 81.3785%.

Integrating Information in Biological Ontologies and Molecular Networks to Infer Novel Terms.

PubMed

Li, Le; Yip, Kevin Y

2016-12-15

Currently most terms and term-term relationships in Gene Ontology (GO) are defined manually, which creates cost, consistency and completeness issues. Recent studies have demonstrated the feasibility of inferring GO automatically from biological networks, which represents an important complementary approach to GO construction. These methods (NeXO and CliXO) are unsupervised, which means 1) they cannot use the information contained in existing GO, 2) the way they integrate biological networks may not optimize the accuracy, and 3) they are not customized to infer the three different sub-ontologies of GO. Here we present a semi-supervised method called Unicorn that extends these previous methods to tackle the three problems. Unicorn uses a sub-tree of an existing GO sub-ontology as training part to learn parameters in integrating multiple networks. Cross-validation results show that Unicorn reliably inferred the left-out parts of each specific GO sub-ontology. In addition, by training Unicorn with an old version of GO together with biological networks, it successfully re-discovered some terms and term-term relationships present only in a new version of GO. Unicorn also successfully inferred some novel terms that were not contained in GO but have biological meanings well-supported by the literature. Source code of Unicorn is available at http://yiplab.cse.cuhk.edu.hk/unicorn/.
Social representations and contextual adjustments as two distinct components of the Theory of Mind brain network: Evidence from the REMICS task.

PubMed

Lavoie, Marie-Audrey; Vistoli, Damien; Sutliff, Stephanie; Jackson, Philip L; Achim, Amélie M

2016-08-01

Theory of mind (ToM) refers to the ability to infer the mental states of others. Behavioral measures of ToM usually present information about both a character and the context in which this character is placed, and these different pieces of information can be used to infer the character's mental states. A set of brain regions designated as the ToM brain network is recognized to support (ToM) inferences. Different brain regions within that network could however support different ToM processes. This functional magnetic resonance imaging (fMRI) study aimed to distinguish the brain regions supporting two aspects inherent to many ToM tasks, i.e., the ability to infer or represent mental states and the ability to use the context to adjust these inferences. Nineteen healthy subjects were scanned during the REMICS task, a novel task designed to orthogonally manipulate mental state inferences (as opposed to physical inferences) and contextual adjustments of inferences (as opposed to inferences that do not require contextual adjustments). We observed that mental state inferences and contextual adjustments, which are important aspects of most behavioral ToM tasks, rely on distinct brain regions or subregions within the classical brain network activated in previous ToM research. Notably, an interesting dissociation emerged within the medial prefrontal cortex (mPFC) and temporo-parietal junctions (TPJ) such that the inferior part of these brain regions responded to mental state inferences while the superior part of these brain regions responded to the requirement for contextual adjustments. This study provides evidence that the overall set of brain regions activated during ToM tasks supports different processes, and highlights that cognitive processes related to contextual adjustments have an important role in ToM and should be further studied. Copyright © 2016 Elsevier Ltd. All rights reserved.
TMA Navigator: network inference, patient stratification and survival analysis with tissue microarray data

PubMed Central

Lubbock, Alexander L. R.; Katz, Elad; Harrison, David J.; Overton, Ian M.

2013-01-01

Tissue microarrays (TMAs) allow multiplexed analysis of tissue samples and are frequently used to estimate biomarker protein expression in tumour biopsies. TMA Navigator (www.tmanavigator.org) is an open access web application for analysis of TMA data and related information, accommodating categorical, semi-continuous and continuous expression scores. Non-biological variation, or batch effects, can hinder data analysis and may be mitigated using the ComBat algorithm, which is incorporated with enhancements for automated application to TMA data. Unsupervised grouping of samples (patients) is provided according to Gaussian mixture modelling of marker scores, with cardinality selected by Bayesian information criterion regularization. Kaplan–Meier survival analysis is available, including comparison of groups identified by mixture modelling using the Mantel-Cox log-rank test. TMA Navigator also supports network inference approaches useful for TMA datasets, which often constitute comparatively few markers. Tissue and cell-type specific networks derived from TMA expression data offer insights into the molecular logic underlying pathophenotypes, towards more effective and personalized medicine. Output is interactive, and results may be exported for use with external programs. Private anonymous access is available, and user accounts may be generated for easier data management. PMID:23761446
Analysis and Design of Complex Network Environments

DTIC Science & Technology

2014-02-01

entanglements among un- measured variables. This “potential entanglement ” type of network complexity is previously unaddressed in the literature, yet it...Appreciating the power of structural representations that allow for potential entanglement among unmeasured variables to simplify network inference problems...rely on the idea of subsystems and allows for potential entanglement among unmeasured states. As a result, inferring a system’s signal structure
TernaryNet: faster deep model inference without GPUs for medical 3D segmentation using sparse and binary convolutions.

PubMed

Heinrich, Mattias P; Blendowski, Max; Oktay, Ozan

2018-05-30

Deep convolutional neural networks (DCNN) are currently ubiquitous in medical imaging. While their versatility and high-quality results for common image analysis tasks including segmentation, localisation and prediction is astonishing, the large representational power comes at the cost of highly demanding computational effort. This limits their practical applications for image-guided interventions and diagnostic (point-of-care) support using mobile devices without graphics processing units (GPU). We propose a new scheme that approximates both trainable weights and neural activations in deep networks by ternary values and tackles the open question of backpropagation when dealing with non-differentiable functions. Our solution enables the removal of the expensive floating-point matrix multiplications throughout any convolutional neural network and replaces them by energy- and time-preserving binary operators and population counts. We evaluate our approach for the segmentation of the pancreas in CT. Here, our ternary approximation within a fully convolutional network leads to more than 90% memory reductions and high accuracy (without any post-processing) with a Dice overlap of 71.0% that comes close to the one obtained when using networks with high-precision weights and activations. We further provide a concept for sub-second inference without GPUs and demonstrate significant improvements in comparison with binary quantisation and without our proposed ternary hyperbolic tangent continuation. We present a key enabling technique for highly efficient DCNN inference without GPUs that will help to bring the advances of deep learning to practical clinical applications. It has also great promise for improving accuracies in large-scale medical data retrieval.
Inferring topologies via driving-based generalized synchronization of two-layer networks

NASA Astrophysics Data System (ADS)

Wang, Yingfei; Wu, Xiaoqun; Feng, Hui; Lu, Jun-an; Xu, Yuhua

2016-05-01

The interaction topology among the constituents of a complex network plays a crucial role in the network’s evolutionary mechanisms and functional behaviors. However, some network topologies are usually unknown or uncertain. Meanwhile, coupling delays are ubiquitous in various man-made and natural networks. Hence, it is necessary to gain knowledge of the whole or partial topology of a complex dynamical network by taking into consideration communication delay. In this paper, topology identification of complex dynamical networks is investigated via generalized synchronization of a two-layer network. Particularly, based on the LaSalle-type invariance principle of stochastic differential delay equations, an adaptive control technique is proposed by constructing an auxiliary layer and designing proper control input and updating laws so that the unknown topology can be recovered upon successful generalized synchronization. Numerical simulations are provided to illustrate the effectiveness of the proposed method. The technique provides a certain theoretical basis for topology inference of complex networks. In particular, when the considered network is composed of systems with high-dimension or complicated dynamics, a simpler response layer can be constructed, which is conducive to circuit design. Moreover, it is practical to take into consideration perturbations caused by control input. Finally, the method is applicable to infer topology of a subnetwork embedded within a complex system and locate hidden sources. We hope the results can provide basic insight into further research endeavors on understanding practical and economical topology inference of networks.
Planetary micro-rover operations on Mars using a Bayesian framework for inference and control

NASA Astrophysics Data System (ADS)

Post, Mark A.; Li, Junquan; Quine, Brendan M.

2016-03-01

With the recent progress toward the application of commercially-available hardware to small-scale space missions, it is now becoming feasible for groups of small, efficient robots based on low-power embedded hardware to perform simple tasks on other planets in the place of large-scale, heavy and expensive robots. In this paper, we describe design and programming of the Beaver micro-rover developed for Northern Light, a Canadian initiative to send a small lander and rover to Mars to study the Martian surface and subsurface. For a small, hardware-limited rover to handle an uncertain and mostly unknown environment without constant management by human operators, we use a Bayesian network of discrete random variables as an abstraction of expert knowledge about the rover and its environment, and inference operations for control. A framework for efficient construction and inference into a Bayesian network using only the C language and fixed-point mathematics on embedded hardware has been developed for the Beaver to make intelligent decisions with minimal sensor data. We study the performance of the Beaver as it probabilistically maps a simple outdoor environment with sensor models that include uncertainty. Results indicate that the Beaver and other small and simple robotic platforms can make use of a Bayesian network to make intelligent decisions in uncertain planetary environments.
Inference of genetic network of Xenopus frog egg: improved genetic algorithm.

PubMed

Wu, Shinq-Jen; Chou, Chia-Hsien; Wu, Cheng-Tao; Lee, Tsu-Tian

2006-01-01

An improved genetic algorithm (IGA) is proposed to achieve S-system gene network modeling of Xenopus frog egg. Via the time-courses training datasets from Michaelis-Menten model, the optimal parameters are learned. The S-system can clearly describe activative and inhibitory interaction between genes as generating and consuming process. We concern the mitotic control in cell-cycle of Xenopus frog egg to realize cyclin-Cdc2 and Cdc25 for MPF activity. The proposed IGA can achieve global search with migration and keep the best chromosome with elitism operation. The generated gene regulatory networks can provide biological researchers for further experiments in Xenopus frog egg cell cycle control.
Bayesian inference for dynamic transcriptional regulation; the Hes1 system as a case study.

PubMed

Heron, Elizabeth A; Finkenstädt, Bärbel; Rand, David A

2007-10-01

In this study, we address the problem of estimating the parameters of regulatory networks and provide the first application of Markov chain Monte Carlo (MCMC) methods to experimental data. As a case study, we consider a stochastic model of the Hes1 system expressed in terms of stochastic differential equations (SDEs) to which rigorous likelihood methods of inference can be applied. When fitting continuous-time stochastic models to discretely observed time series the lengths of the sampling intervals are important, and much of our study addresses the problem when the data are sparse. We estimate the parameters of an autoregulatory network providing results both for simulated and real experimental data from the Hes1 system. We develop an estimation algorithm using MCMC techniques which are flexible enough to allow for the imputation of latent data on a finer time scale and the presence of prior information about parameters which may be informed from other experiments as well as additional measurement error.
Evidence reasoning method for constructing conditional probability tables in a Bayesian network of multimorbidity.

PubMed

Du, Yuanwei; Guo, Yubin

2015-01-01

The intrinsic mechanism of multimorbidity is difficult to recognize and prediction and diagnosis are difficult to carry out accordingly. Bayesian networks can help to diagnose multimorbidity in health care, but it is difficult to obtain the conditional probability table (CPT) because of the lack of clinically statistical data. Today, expert knowledge and experience are increasingly used in training Bayesian networks in order to help predict or diagnose diseases, but the CPT in Bayesian networks is usually irrational or ineffective for ignoring realistic constraints especially in multimorbidity. In order to solve these problems, an evidence reasoning (ER) approach is employed to extract and fuse inference data from experts using a belief distribution and recursive ER algorithm, based on which evidence reasoning method for constructing conditional probability tables in Bayesian network of multimorbidity is presented step by step. A multimorbidity numerical example is used to demonstrate the method and prove its feasibility and application. Bayesian network can be determined as long as the inference assessment is inferred by each expert according to his/her knowledge or experience. Our method is more effective than existing methods for extracting expert inference data accurately and is fused effectively for constructing CPTs in a Bayesian network of multimorbidity.
Inference of financial networks using the normalised mutual information rate.

PubMed

Goh, Yong Kheng; Hasim, Haslifah M; Antonopoulos, Chris G

2018-01-01

In this paper, we study data from financial markets, using the normalised Mutual Information Rate. We show how to use it to infer the underlying network structure of interrelations in the foreign currency exchange rates and stock indices of 15 currency areas. We first present the mathematical method and discuss its computational aspects, and apply it to artificial data from chaotic dynamics and to correlated normal-variates data. We then apply the method to infer the structure of the financial system from the time-series of currency exchange rates and stock indices. In particular, we study and reveal the interrelations among the various foreign currency exchange rates and stock indices in two separate networks, of which we also study their structural properties. Our results show that both inferred networks are small-world networks, sharing similar properties and having differences in terms of assortativity. Importantly, our work shows that global economies tend to connect with other economies world-wide, rather than creating small groups of local economies. Finally, the consistent interrelations depicted among the 15 currency areas are further supported by a discussion from the viewpoint of economics.
Inference of financial networks using the normalised mutual information rate

PubMed Central

2018-01-01

In this paper, we study data from financial markets, using the normalised Mutual Information Rate. We show how to use it to infer the underlying network structure of interrelations in the foreign currency exchange rates and stock indices of 15 currency areas. We first present the mathematical method and discuss its computational aspects, and apply it to artificial data from chaotic dynamics and to correlated normal-variates data. We then apply the method to infer the structure of the financial system from the time-series of currency exchange rates and stock indices. In particular, we study and reveal the interrelations among the various foreign currency exchange rates and stock indices in two separate networks, of which we also study their structural properties. Our results show that both inferred networks are small-world networks, sharing similar properties and having differences in terms of assortativity. Importantly, our work shows that global economies tend to connect with other economies world-wide, rather than creating small groups of local economies. Finally, the consistent interrelations depicted among the 15 currency areas are further supported by a discussion from the viewpoint of economics. PMID:29420644
Functional mechanisms of probabilistic inference in feature- and space-based attentional systems.

PubMed

Dombert, Pascasie L; Kuhns, Anna; Mengotti, Paola; Fink, Gereon R; Vossel, Simone

2016-11-15

Humans flexibly attend to features or locations and these processes are influenced by the probability of sensory events. We combined computational modeling of response times with fMRI to compare the functional correlates of (re-)orienting, and the modulation by probabilistic inference in spatial and feature-based attention systems. Twenty-four volunteers performed two task versions with spatial or color cues. Percentage of cue validity changed unpredictably. A hierarchical Bayesian model was used to derive trial-wise estimates of probability-dependent attention, entering the fMRI analysis as parametric regressors. Attentional orienting activated a dorsal frontoparietal network in both tasks, without significant parametric modulation. Spatially invalid trials activated a bilateral frontoparietal network and the precuneus, while invalid feature trials activated the left intraparietal sulcus (IPS). Probability-dependent attention modulated activity in the precuneus, left posterior IPS, middle occipital gyrus, and right temporoparietal junction for spatial attention, and in the left anterior IPS for feature-based and spatial attention. These findings provide novel insights into the generality and specificity of the functional basis of attentional control. They suggest that probabilistic inference can distinctively affect each attentional subsystem, but that there is an overlap in the left IPS, which responds to both spatial and feature-based expectancy violations. Copyright © 2016 Elsevier Inc. All rights reserved.
Inferring a District-Based Hierarchical Structure of Social Contacts from Census Data

PubMed Central

Yu, Zhiwen; Liu, Jiming; Zhu, Xianjun

2015-01-01

Researchers have recently paid attention to social contact patterns among individuals due to their useful applications in such areas as epidemic evaluation and control, public health decisions, chronic disease research and social network research. Although some studies have estimated social contact patterns from social networks and surveys, few have considered how to infer the hierarchical structure of social contacts directly from census data. In this paper, we focus on inferring an individual’s social contact patterns from detailed census data, and generate various types of social contact patterns such as hierarchical-district-structure-based, cross-district and age-district-based patterns. We evaluate newly generated contact patterns derived from detailed 2011 Hong Kong census data by incorporating them into a model and simulation of the 2009 Hong Kong H1N1 epidemic. We then compare the newly generated social contact patterns with the mixing patterns that are often used in the literature, and draw the following conclusions. First, the generation of social contact patterns based on a hierarchical district structure allows for simulations at different district levels. Second, the newly generated social contact patterns reflect individuals social contacts. Third, the newly generated social contact patterns improve the accuracy of the SEIR-based epidemic model. PMID:25679787
A sub-space greedy search method for efficient Bayesian Network inference.

PubMed

Zhang, Qing; Cao, Yong; Li, Yong; Zhu, Yanming; Sun, Samuel S M; Guo, Dianjing

2011-09-01

Bayesian network (BN) has been successfully used to infer the regulatory relationships of genes from microarray dataset. However, one major limitation of BN approach is the computational cost because the calculation time grows more than exponentially with the dimension of the dataset. In this paper, we propose a sub-space greedy search method for efficient Bayesian Network inference. Particularly, this method limits the greedy search space by only selecting gene pairs with higher partial correlation coefficients. Using both synthetic and real data, we demonstrate that the proposed method achieved comparable results with standard greedy search method yet saved ∼50% of the computational time. We believe that sub-space search method can be widely used for efficient BN inference in systems biology. Copyright © 2011 Elsevier Ltd. All rights reserved.
Mobile Context Provider for Social Networking

NASA Astrophysics Data System (ADS)

Santos, André C.; Cardoso, João M. P.; Ferreira, Diogo R.; Diniz, Pedro C.

The ability to infer user context based on a mobile device together with a set of external sensors opens up the way to new context-aware services and applications. In this paper, we describe a mobile context provider that makes use of sensors available in a smartphone as well as sensors externally connected via bluetooth. We describe the system architecture from sensor data acquisition to feature extraction, context inference and the publication of context information to well-known social networking services such as Twitter and Hi5. In the current prototype, context inference is based on decision trees, but the middleware allows the integration of other inference engines. Experimental results suggest that the proposed solution is a promising approach to provide user context to both local and network-level services.
Network inference and network response identification: moving genome-scale data to the next level of biological discovery

PubMed Central

Veiga, Diogo F. T.; Dutta, Bhaskar; Balaźsi, Gábor

2011-01-01

The escalating amount of genome-scale data demands a pragmatic stance from the research community. How can we utilize this deluge of information to better understand biology, cure diseases, or engage cells in bioremediation or biomaterial production for various purposes? A research pipeline moving new sequence, expression and binding data towards practical end goals seems to be necessary. While most individual researchers are not motivated by such well-articulated pragmatic end goals, the scientific community has already self-organized itself to successfully convert genomic data into fundamentally new biological knowledge and practical applications. Here we review two important steps in this workflow: network inference and network response identification, applied to transcriptional regulatory networks. Among network inference methods, we concentrate on relevance networks due to their conceptual simplicity. We classify and discuss network response identification approaches as either data-centric or network-centric. Finally, we conclude with an outlook on what is still missing from these approaches and what may be ahead on the road to biological discovery. PMID:20174676
Inference of Expanded Lrp-Like Feast/Famine Transcription Factor Targets in a Non-Model Organism Using Protein Structure-Based Prediction

PubMed Central

Ashworth, Justin; Plaisier, Christopher L.; Lo, Fang Yin; Reiss, David J.; Baliga, Nitin S.

2014-01-01

Widespread microbial genome sequencing presents an opportunity to understand the gene regulatory networks of non-model organisms. This requires knowledge of the binding sites for transcription factors whose DNA-binding properties are unknown or difficult to infer. We adapted a protein structure-based method to predict the specificities and putative regulons of homologous transcription factors across diverse species. As a proof-of-concept we predicted the specificities and transcriptional target genes of divergent archaeal feast/famine regulatory proteins, several of which are encoded in the genome of Halobacterium salinarum. This was validated by comparison to experimentally determined specificities for transcription factors in distantly related extremophiles, chromatin immunoprecipitation experiments, and cis-regulatory sequence conservation across eighteen related species of halobacteria. Through this analysis we were able to infer that Halobacterium salinarum employs a divergent local trans-regulatory strategy to regulate genes (carA and carB) involved in arginine and pyrimidine metabolism, whereas Escherichia coli employs an operon. The prediction of gene regulatory binding sites using structure-based methods is useful for the inference of gene regulatory relationships in new species that are otherwise difficult to infer. PMID:25255272
Inference of expanded Lrp-like feast/famine transcription factor targets in a non-model organism using protein structure-based prediction.

PubMed

Ashworth, Justin; Plaisier, Christopher L; Lo, Fang Yin; Reiss, David J; Baliga, Nitin S

2014-01-01

Widespread microbial genome sequencing presents an opportunity to understand the gene regulatory networks of non-model organisms. This requires knowledge of the binding sites for transcription factors whose DNA-binding properties are unknown or difficult to infer. We adapted a protein structure-based method to predict the specificities and putative regulons of homologous transcription factors across diverse species. As a proof-of-concept we predicted the specificities and transcriptional target genes of divergent archaeal feast/famine regulatory proteins, several of which are encoded in the genome of Halobacterium salinarum. This was validated by comparison to experimentally determined specificities for transcription factors in distantly related extremophiles, chromatin immunoprecipitation experiments, and cis-regulatory sequence conservation across eighteen related species of halobacteria. Through this analysis we were able to infer that Halobacterium salinarum employs a divergent local trans-regulatory strategy to regulate genes (carA and carB) involved in arginine and pyrimidine metabolism, whereas Escherichia coli employs an operon. The prediction of gene regulatory binding sites using structure-based methods is useful for the inference of gene regulatory relationships in new species that are otherwise difficult to infer.
Exploiting combinatorial cultivation conditions to infer transcriptional regulation

PubMed Central

Knijnenburg, Theo A; de Winde, Johannes H; Daran, Jean-Marc; Daran-Lapujade, Pascale; Pronk, Jack T; Reinders, Marcel JT; Wessels, Lodewyk FA

2007-01-01

Background Regulatory networks often employ the model that attributes changes in gene expression levels, as observed across different cellular conditions, to changes in the activity of transcription factors (TFs). Although the actual conditions that trigger a change in TF activity should form an integral part of the generated regulatory network, they are usually lacking. This is due to the fact that the large heterogeneity in the employed conditions and the continuous changes in environmental parameters in the often used shake-flask cultures, prevent the unambiguous modeling of the cultivation conditions within the computational framework. Results We designed an experimental setup that allows us to explicitly model the cultivation conditions and use these to infer the activity of TFs. The yeast Saccharomyces cerevisiae was cultivated under four different nutrient limitations in both aerobic and anaerobic chemostat cultures. In the chemostats, environmental and growth parameters are accurately controlled. Consequently, the measured transcriptional response can be directly correlated with changes in the limited nutrient or oxygen concentration. We devised a tailor-made computational approach that exploits the systematic setup of the cultivation conditions in order to identify the individual and combined effects of nutrient limitations and oxygen availability on expression behavior and TF activity. Conclusion Incorporating the actual growth conditions when inferring regulatory relationships provides detailed insight in the functionality of the TFs that are triggered by changes in the employed cultivation conditions. For example, our results confirm the established role of TF Hap4 in both aerobic regulation and glucose derepression. Among the numerous inferred condition-specific regulatory associations between gene sets and TFs, also many novel putative regulatory mechanisms, such as the possible role of Tye7 in sulfur metabolism, were identified. PMID:17241460

Exploiting combinatorial cultivation conditions to infer transcriptional regulation.

PubMed

Knijnenburg, Theo A; de Winde, Johannes H; Daran, Jean-Marc; Daran-Lapujade, Pascale; Pronk, Jack T; Reinders, Marcel J T; Wessels, Lodewyk F A

2007-01-22

Regulatory networks often employ the model that attributes changes in gene expression levels, as observed across different cellular conditions, to changes in the activity of transcription factors (TFs). Although the actual conditions that trigger a change in TF activity should form an integral part of the generated regulatory network, they are usually lacking. This is due to the fact that the large heterogeneity in the employed conditions and the continuous changes in environmental parameters in the often used shake-flask cultures, prevent the unambiguous modeling of the cultivation conditions within the computational framework. We designed an experimental setup that allows us to explicitly model the cultivation conditions and use these to infer the activity of TFs. The yeast Saccharomyces cerevisiae was cultivated under four different nutrient limitations in both aerobic and anaerobic chemostat cultures. In the chemostats, environmental and growth parameters are accurately controlled. Consequently, the measured transcriptional response can be directly correlated with changes in the limited nutrient or oxygen concentration. We devised a tailor-made computational approach that exploits the systematic setup of the cultivation conditions in order to identify the individual and combined effects of nutrient limitations and oxygen availability on expression behavior and TF activity. Incorporating the actual growth conditions when inferring regulatory relationships provides detailed insight in the functionality of the TFs that are triggered by changes in the employed cultivation conditions. For example, our results confirm the established role of TF Hap4 in both aerobic regulation and glucose derepression. Among the numerous inferred condition-specific regulatory associations between gene sets and TFs, also many novel putative regulatory mechanisms, such as the possible role of Tye7 in sulfur metabolism, were identified.
Social network models predict movement and connectivity in ecological landscapes

USGS Publications Warehouse

Fletcher, R.J.; Acevedo, M.A.; Reichert, Brian E.; Pias, Kyle E.; Kitchens, W.M.

2011-01-01

Network analysis is on the rise across scientific disciplines because of its ability to reveal complex, and often emergent, patterns and dynamics. Nonetheless, a growing concern in network analysis is the use of limited data for constructing networks. This concern is strikingly relevant to ecology and conservation biology, where network analysis is used to infer connectivity across landscapes. In this context, movement among patches is the crucial parameter for interpreting connectivity but because of the difficulty of collecting reliable movement data, most network analysis proceeds with only indirect information on movement across landscapes rather than using observed movement to construct networks. Statistical models developed for social networks provide promising alternatives for landscape network construction because they can leverage limited movement information to predict linkages. Using two mark-recapture datasets on individual movement and connectivity across landscapes, we test whether commonly used network constructions for interpreting connectivity can predict actual linkages and network structure, and we contrast these approaches to social network models. We find that currently applied network constructions for assessing connectivity consistently, and substantially, overpredict actual connectivity, resulting in considerable overestimation of metapopulation lifetime. Furthermore, social network models provide accurate predictions of network structure, and can do so with remarkably limited data on movement. Social network models offer a flexible and powerful way for not only understanding the factors influencing connectivity but also for providing more reliable estimates of connectivity and metapopulation persistence in the face of limited data.
A Prize-Collecting Steiner Tree Approach for Transduction Network Inference

NASA Astrophysics Data System (ADS)

Bailly-Bechet, Marc; Braunstein, Alfredo; Zecchina, Riccardo

Into the cell, information from the environment is mainly propagated via signaling pathways which form a transduction network. Here we propose a new algorithm to infer transduction networks from heterogeneous data, using both the protein interaction network and expression datasets. We formulate the inference problem as an optimization task, and develop a message-passing, probabilistic and distributed formalism to solve it. We apply our algorithm to the pheromone response in the baker’s yeast S. cerevisiae. We are able to find the backbone of the known structure of the MAPK cascade of pheromone response, validating our algorithm. More importantly, we make biological predictions about some proteins whose role could be at the interface between pheromone response and other cellular functions.
Artificial neural network modeling of dissolved oxygen in reservoir.

PubMed

Chen, Wei-Bo; Liu, Wen-Cheng

2014-02-01

The water quality of reservoirs is one of the key factors in the operation and water quality management of reservoirs. Dissolved oxygen (DO) in water column is essential for microorganisms and a significant indicator of the state of aquatic ecosystems. In this study, two artificial neural network (ANN) models including back propagation neural network (BPNN) and adaptive neural-based fuzzy inference system (ANFIS) approaches and multilinear regression (MLR) model were developed to estimate the DO concentration in the Feitsui Reservoir of northern Taiwan. The input variables of the neural network are determined as water temperature, pH, conductivity, turbidity, suspended solids, total hardness, total alkalinity, and ammonium nitrogen. The performance of the ANN models and MLR model was assessed through the mean absolute error, root mean square error, and correlation coefficient computed from the measured and model-simulated DO values. The results reveal that ANN estimation performances were superior to those of MLR. Comparing to the BPNN and ANFIS models through the performance criteria, the ANFIS model is better than the BPNN model for predicting the DO values. Study results show that the neural network particularly using ANFIS model is able to predict the DO concentrations with reasonable accuracy, suggesting that the neural network is a valuable tool for reservoir management in Taiwan.
Embodied learning of a generative neural model for biological motion perception and inference

PubMed Central

Schrodt, Fabian; Layher, Georg; Neumann, Heiko; Butz, Martin V.

2015-01-01

Although an action observation network and mirror neurons for understanding the actions and intentions of others have been under deep, interdisciplinary consideration over recent years, it remains largely unknown how the brain manages to map visually perceived biological motion of others onto its own motor system. This paper shows how such a mapping may be established, even if the biologically motion is visually perceived from a new vantage point. We introduce a learning artificial neural network model and evaluate it on full body motion tracking recordings. The model implements an embodied, predictive inference approach. It first learns to correlate and segment multimodal sensory streams of own bodily motion. In doing so, it becomes able to anticipate motion progression, to complete missing modal information, and to self-generate learned motion sequences. When biological motion of another person is observed, this self-knowledge is utilized to recognize similar motion patterns and predict their progress. Due to the relative encodings, the model shows strong robustness in recognition despite observing rather large varieties of body morphology and posture dynamics. By additionally equipping the model with the capability to rotate its visual frame of reference, it is able to deduce the visual perspective onto the observed person, establishing full consistency to the embodied self-motion encodings by means of active inference. In further support of its neuro-cognitive plausibility, we also model typical bistable perceptions when crucial depth information is missing. In sum, the introduced neural model proposes a solution to the problem of how the human brain may establish correspondence between observed bodily motion and its own motor system, thus offering a mechanism that supports the development of mirror neurons. PMID:26217215
Embodied learning of a generative neural model for biological motion perception and inference.

PubMed

Schrodt, Fabian; Layher, Georg; Neumann, Heiko; Butz, Martin V

2015-01-01

Although an action observation network and mirror neurons for understanding the actions and intentions of others have been under deep, interdisciplinary consideration over recent years, it remains largely unknown how the brain manages to map visually perceived biological motion of others onto its own motor system. This paper shows how such a mapping may be established, even if the biologically motion is visually perceived from a new vantage point. We introduce a learning artificial neural network model and evaluate it on full body motion tracking recordings. The model implements an embodied, predictive inference approach. It first learns to correlate and segment multimodal sensory streams of own bodily motion. In doing so, it becomes able to anticipate motion progression, to complete missing modal information, and to self-generate learned motion sequences. When biological motion of another person is observed, this self-knowledge is utilized to recognize similar motion patterns and predict their progress. Due to the relative encodings, the model shows strong robustness in recognition despite observing rather large varieties of body morphology and posture dynamics. By additionally equipping the model with the capability to rotate its visual frame of reference, it is able to deduce the visual perspective onto the observed person, establishing full consistency to the embodied self-motion encodings by means of active inference. In further support of its neuro-cognitive plausibility, we also model typical bistable perceptions when crucial depth information is missing. In sum, the introduced neural model proposes a solution to the problem of how the human brain may establish correspondence between observed bodily motion and its own motor system, thus offering a mechanism that supports the development of mirror neurons.
Inferring gene and protein interactions using PubMed citations and consensus Bayesian networks

PubMed Central

Dalman, Mark; Haddad, Joseph; Duan, Zhong-Hui

2017-01-01

The PubMed database offers an extensive set of publication data that can be useful, yet inherently complex to use without automated computational techniques. Data repositories such as the Genomic Data Commons (GDC) and the Gene Expression Omnibus (GEO) offer experimental data storage and retrieval as well as curated gene expression profiles. Genetic interaction databases, including Reactome and Ingenuity Pathway Analysis, offer pathway and experiment data analysis using data curated from these publications and data repositories. We have created a method to generate and analyze consensus networks, inferring potential gene interactions, using large numbers of Bayesian networks generated by data mining publications in the PubMed database. Through the concept of network resolution, these consensus networks can be tailored to represent possible genetic interactions. We designed a set of experiments to confirm that our method is stable across variation in both sample and topological input sizes. Using gene product interactions from the KEGG pathway database and data mining PubMed publication abstracts, we verify that regardless of the network resolution or the inferred consensus network, our method is capable of inferring meaningful gene interactions through consensus Bayesian network generation with multiple, randomized topological orderings. Our method can not only confirm the existence of currently accepted interactions, but has the potential to hypothesize new ones as well. We show our method confirms the existence of known gene interactions such as JAK-STAT-PI3K-AKT-mTOR, infers novel gene interactions such as RAS- Bcl-2 and RAS-AKT, and found significant pathway-pathway interactions between the JAK-STAT signaling and Cardiac Muscle Contraction KEGG pathways. PMID:29049295
Inferring Boolean network states from partial information

PubMed Central

2013-01-01

Networks of molecular interactions regulate key processes in living cells. Therefore, understanding their functionality is a high priority in advancing biological knowledge. Boolean networks are often used to describe cellular networks mathematically and are fitted to experimental datasets. The fitting often results in ambiguities since the interpretation of the measurements is not straightforward and since the data contain noise. In order to facilitate a more reliable mapping between datasets and Boolean networks, we develop an algorithm that infers network trajectories from a dataset distorted by noise. We analyze our algorithm theoretically and demonstrate its accuracy using simulation and microarray expression data. PMID:24006954
Variable neighborhood search for reverse engineering of gene regulatory networks.

PubMed

Nicholson, Charles; Goodwin, Leslie; Clark, Corey

2017-01-01

A new search heuristic, Divided Neighborhood Exploration Search, designed to be used with inference algorithms such as Bayesian networks to improve on the reverse engineering of gene regulatory networks is presented. The approach systematically moves through the search space to find topologies representative of gene regulatory networks that are more likely to explain microarray data. In empirical testing it is demonstrated that the novel method is superior to the widely employed greedy search techniques in both the quality of the inferred networks and computational time. Copyright © 2016 Elsevier Inc. All rights reserved.
Revealing networks from dynamics: an introduction

NASA Astrophysics Data System (ADS)

Timme, Marc; Casadiego, Jose

2014-08-01

What can we learn from the collective dynamics of a complex network about its interaction topology? Taking the perspective from nonlinear dynamics, we briefly review recent progress on how to infer structural connectivity (direct interactions) from accessing the dynamics of the units. Potential applications range from interaction networks in physics, to chemical and metabolic reactions, protein and gene regulatory networks as well as neural circuits in biology and electric power grids or wireless sensor networks in engineering. Moreover, we briefly mention some standard ways of inferring effective or functional connectivity.
On the Structure of Cortical Microcircuits Inferred from Small Sample Sizes.

PubMed

Vegué, Marina; Perin, Rodrigo; Roxin, Alex

2017-08-30

The structure in cortical microcircuits deviates from what would be expected in a purely random network, which has been seen as evidence of clustering. To address this issue, we sought to reproduce the nonrandom features of cortical circuits by considering several distinct classes of network topology, including clustered networks, networks with distance-dependent connectivity, and those with broad degree distributions. To our surprise, we found that all of these qualitatively distinct topologies could account equally well for all reported nonrandom features despite being easily distinguishable from one another at the network level. This apparent paradox was a consequence of estimating network properties given only small sample sizes. In other words, networks that differ markedly in their global structure can look quite similar locally. This makes inferring network structure from small sample sizes, a necessity given the technical difficulty inherent in simultaneous intracellular recordings, problematic. We found that a network statistic called the sample degree correlation (SDC) overcomes this difficulty. The SDC depends only on parameters that can be estimated reliably given small sample sizes and is an accurate fingerprint of every topological family. We applied the SDC criterion to data from rat visual and somatosensory cortex and discovered that the connectivity was not consistent with any of these main topological classes. However, we were able to fit the experimental data with a more general network class, of which all previous topologies were special cases. The resulting network topology could be interpreted as a combination of physical spatial dependence and nonspatial, hierarchical clustering. SIGNIFICANCE STATEMENT The connectivity of cortical microcircuits exhibits features that are inconsistent with a simple random network. Here, we show that several classes of network models can account for this nonrandom structure despite qualitative differences in their global properties. This apparent paradox is a consequence of the small numbers of simultaneously recorded neurons in experiment: when inferred via small sample sizes, many networks may be indistinguishable despite being globally distinct. We develop a connectivity measure that successfully classifies networks even when estimated locally with a few neurons at a time. We show that data from rat cortex is consistent with a network in which the likelihood of a connection between neurons depends on spatial distance and on nonspatial, asymmetric clustering. Copyright © 2017 the authors 0270-6474/17/378498-13$15.00/0.
Multiple hot-deck imputation for network inference from RNA sequencing data.

PubMed

Imbert, Alyssa; Valsesia, Armand; Le Gall, Caroline; Armenise, Claudia; Lefebvre, Gregory; Gourraud, Pierre-Antoine; Viguerie, Nathalie; Villa-Vialaneix, Nathalie

2018-05-15

Network inference provides a global view of the relations existing between gene expression in a given transcriptomic experiment (often only for a restricted list of chosen genes). However, it is still a challenging problem: even if the cost of sequencing techniques has decreased over the last years, the number of samples in a given experiment is still (very) small compared to the number of genes. We propose a method to increase the reliability of the inference when RNA-seq expression data have been measured together with an auxiliary dataset that can provide external information on gene expression similarity between samples. Our statistical approach, hd-MI, is based on imputation for samples without available RNA-seq data that are considered as missing data but are observed on the secondary dataset. hd-MI can improve the reliability of the inference for missing rates up to 30% and provides more stable networks with a smaller number of false positive edges. On a biological point of view, hd-MI was also found relevant to infer networks from RNA-seq data acquired in adipose tissue during a nutritional intervention in obese individuals. In these networks, novel links between genes were highlighted, as well as an improved comparability between the two steps of the nutritional intervention. Software and sample data are available as an R package, RNAseqNet, that can be downloaded from the Comprehensive R Archive Network (CRAN). alyssa.imbert@inra.fr or nathalie.villa-vialaneix@inra.fr. Supplementary data are available at Bioinformatics online.
Inferring nonlinear gene regulatory networks from gene expression data based on distance correlation.

PubMed

Guo, Xiaobo; Zhang, Ye; Hu, Wenhao; Tan, Haizhu; Wang, Xueqin

2014-01-01

Nonlinear dependence is general in regulation mechanism of gene regulatory networks (GRNs). It is vital to properly measure or test nonlinear dependence from real data for reconstructing GRNs and understanding the complex regulatory mechanisms within the cellular system. A recently developed measurement called the distance correlation (DC) has been shown powerful and computationally effective in nonlinear dependence for many situations. In this work, we incorporate the DC into inferring GRNs from the gene expression data without any underling distribution assumptions. We propose three DC-based GRNs inference algorithms: CLR-DC, MRNET-DC and REL-DC, and then compare them with the mutual information (MI)-based algorithms by analyzing two simulated data: benchmark GRNs from the DREAM challenge and GRNs generated by SynTReN network generator, and an experimentally determined SOS DNA repair network in Escherichia coli. According to both the receiver operator characteristic (ROC) curve and the precision-recall (PR) curve, our proposed algorithms significantly outperform the MI-based algorithms in GRNs inference.
Inferring Nonlinear Gene Regulatory Networks from Gene Expression Data Based on Distance Correlation

PubMed Central

Guo, Xiaobo; Zhang, Ye; Hu, Wenhao; Tan, Haizhu; Wang, Xueqin

2014-01-01

Nonlinear dependence is general in regulation mechanism of gene regulatory networks (GRNs). It is vital to properly measure or test nonlinear dependence from real data for reconstructing GRNs and understanding the complex regulatory mechanisms within the cellular system. A recently developed measurement called the distance correlation (DC) has been shown powerful and computationally effective in nonlinear dependence for many situations. In this work, we incorporate the DC into inferring GRNs from the gene expression data without any underling distribution assumptions. We propose three DC-based GRNs inference algorithms: CLR-DC, MRNET-DC and REL-DC, and then compare them with the mutual information (MI)-based algorithms by analyzing two simulated data: benchmark GRNs from the DREAM challenge and GRNs generated by SynTReN network generator, and an experimentally determined SOS DNA repair network in Escherichia coli. According to both the receiver operator characteristic (ROC) curve and the precision-recall (PR) curve, our proposed algorithms significantly outperform the MI-based algorithms in GRNs inference. PMID:24551058
Prediction of Drug-Target Interactions and Drug Repositioning via Network-Based Inference

PubMed Central

Jiang, Jing; Lu, Weiqiang; Li, Weihua; Liu, Guixia; Zhou, Weixing; Huang, Jin; Tang, Yun

2012-01-01

Drug-target interaction (DTI) is the basis of drug discovery and design. It is time consuming and costly to determine DTI experimentally. Hence, it is necessary to develop computational methods for the prediction of potential DTI. Based on complex network theory, three supervised inference methods were developed here to predict DTI and used for drug repositioning, namely drug-based similarity inference (DBSI), target-based similarity inference (TBSI) and network-based inference (NBI). Among them, NBI performed best on four benchmark data sets. Then a drug-target network was created with NBI based on 12,483 FDA-approved and experimental drug-target binary links, and some new DTIs were further predicted. In vitro assays confirmed that five old drugs, namely montelukast, diclofenac, simvastatin, ketoconazole, and itraconazole, showed polypharmacological features on estrogen receptors or dipeptidyl peptidase-IV with half maximal inhibitory or effective concentration ranged from 0.2 to 10 µM. Moreover, simvastatin and ketoconazole showed potent antiproliferative activities on human MDA-MB-231 breast cancer cell line in MTT assays. The results indicated that these methods could be powerful tools in prediction of DTIs and drug repositioning. PMID:22589709
Daily water level forecasting using wavelet decomposition and artificial intelligence techniques

NASA Astrophysics Data System (ADS)

Seo, Youngmin; Kim, Sungwon; Kisi, Ozgur; Singh, Vijay P.

2015-01-01

Reliable water level forecasting for reservoir inflow is essential for reservoir operation. The objective of this paper is to develop and apply two hybrid models for daily water level forecasting and investigate their accuracy. These two hybrid models are wavelet-based artificial neural network (WANN) and wavelet-based adaptive neuro-fuzzy inference system (WANFIS). Wavelet decomposition is employed to decompose an input time series into approximation and detail components. The decomposed time series are used as inputs to artificial neural networks (ANN) and adaptive neuro-fuzzy inference system (ANFIS) for WANN and WANFIS models, respectively. Based on statistical performance indexes, the WANN and WANFIS models are found to produce better efficiency than the ANN and ANFIS models. WANFIS7-sym10 yields the best performance among all other models. It is found that wavelet decomposition improves the accuracy of ANN and ANFIS. This study evaluates the accuracy of the WANN and WANFIS models for different mother wavelets, including Daubechies, Symmlet and Coiflet wavelets. It is found that the model performance is dependent on input sets and mother wavelets, and the wavelet decomposition using mother wavelet, db10, can further improve the efficiency of ANN and ANFIS models. Results obtained from this study indicate that the conjunction of wavelet decomposition and artificial intelligence models can be a useful tool for accurate forecasting daily water level and can yield better efficiency than the conventional forecasting models.
Travel Time Estimation Using Freeway Point Detector Data Based on Evolving Fuzzy Neural Inference System.

PubMed

Tang, Jinjun; Zou, Yajie; Ash, John; Zhang, Shen; Liu, Fang; Wang, Yinhai

2016-01-01

Travel time is an important measurement used to evaluate the extent of congestion within road networks. This paper presents a new method to estimate the travel time based on an evolving fuzzy neural inference system. The input variables in the system are traffic flow data (volume, occupancy, and speed) collected from loop detectors located at points both upstream and downstream of a given link, and the output variable is the link travel time. A first order Takagi-Sugeno fuzzy rule set is used to complete the inference. For training the evolving fuzzy neural network (EFNN), two learning processes are proposed: (1) a K-means method is employed to partition input samples into different clusters, and a Gaussian fuzzy membership function is designed for each cluster to measure the membership degree of samples to the cluster centers. As the number of input samples increases, the cluster centers are modified and membership functions are also updated; (2) a weighted recursive least squares estimator is used to optimize the parameters of the linear functions in the Takagi-Sugeno type fuzzy rules. Testing datasets consisting of actual and simulated data are used to test the proposed method. Three common criteria including mean absolute error (MAE), root mean square error (RMSE), and mean absolute relative error (MARE) are utilized to evaluate the estimation performance. Estimation results demonstrate the accuracy and effectiveness of the EFNN method through comparison with existing methods including: multiple linear regression (MLR), instantaneous model (IM), linear model (LM), neural network (NN), and cumulative plots (CP).
Travel Time Estimation Using Freeway Point Detector Data Based on Evolving Fuzzy Neural Inference System

PubMed Central

Tang, Jinjun; Zou, Yajie; Ash, John; Zhang, Shen; Liu, Fang; Wang, Yinhai

2016-01-01

Travel time is an important measurement used to evaluate the extent of congestion within road networks. This paper presents a new method to estimate the travel time based on an evolving fuzzy neural inference system. The input variables in the system are traffic flow data (volume, occupancy, and speed) collected from loop detectors located at points both upstream and downstream of a given link, and the output variable is the link travel time. A first order Takagi-Sugeno fuzzy rule set is used to complete the inference. For training the evolving fuzzy neural network (EFNN), two learning processes are proposed: (1) a K-means method is employed to partition input samples into different clusters, and a Gaussian fuzzy membership function is designed for each cluster to measure the membership degree of samples to the cluster centers. As the number of input samples increases, the cluster centers are modified and membership functions are also updated; (2) a weighted recursive least squares estimator is used to optimize the parameters of the linear functions in the Takagi-Sugeno type fuzzy rules. Testing datasets consisting of actual and simulated data are used to test the proposed method. Three common criteria including mean absolute error (MAE), root mean square error (RMSE), and mean absolute relative error (MARE) are utilized to evaluate the estimation performance. Estimation results demonstrate the accuracy and effectiveness of the EFNN method through comparison with existing methods including: multiple linear regression (MLR), instantaneous model (IM), linear model (LM), neural network (NN), and cumulative plots (CP). PMID:26829639
Inconsistencies in spontaneous and intentional trait inferences.

PubMed

Ma, Ning; Vandekerckhove, Marie; Baetens, Kris; Van Overwalle, Frank; Seurinck, Ruth; Fias, Wim

2012-11-01

This study explores the fMRI correlates of observers making trait inferences about other people under conflicting social cues. Participants were presented with several behavioral descriptions involving an agent that implied a particular trait. The last behavior was either consistent or inconsistent with the previously implied trait. This was done under instructions that elicited either spontaneous trait inferences ('read carefully') or intentional trait inferences ('infer a trait'). The results revealed that when the behavioral descriptions violated earlier trait implications, regardless of instruction, the medial prefrontal cortex (mPFC) was more strongly recruited as well as the domain-general conflict network including the posterior medial frontal cortex (pmFC) and the right prefrontal cortex (rPFC). These latter two areas were more strongly activated under intentional than spontaneous instructions. These findings suggest that when trait-relevant behavioral information is inconsistent, not only is activity increased in the mentalizing network responsible for trait processing, but control is also passed to a higher level conflict monitoring network in order to detect and resolve the contradiction.
System Model Network for Adipose Tissue Signatures Related to Weight Changes in Response to Calorie Restriction and Subsequent Weight Maintenance

PubMed Central

Montastier, Emilie; Villa-Vialaneix, Nathalie; Caspar-Bauguil, Sylvie; Hlavaty, Petr; Tvrzicka, Eva; Gonzalez, Ignacio; Saris, Wim H. M.; Langin, Dominique; Kunesova, Marie; Viguerie, Nathalie

2015-01-01

Nutrigenomics investigates relationships between nutrients and all genome-encoded molecular entities. This holistic approach requires systems biology to scrutinize the effects of diet on tissue biology. To decipher the adipose tissue (AT) response to diet induced weight changes we focused on key molecular (lipids and transcripts) AT species during a longitudinal dietary intervention. To obtain a systems model, a network approach was used to combine all sets of variables (bio-clinical, fatty acids and mRNA levels) and get an overview of their interactions. AT fatty acids and mRNA levels were quantified in 135 obese women at baseline, after an 8-week low calorie diet (LCD) and after 6 months of ad libitum weight maintenance diet (WMD). After LCD, individuals were stratified a posteriori according to weight change during WMD. A 3 steps approach was used to infer a global model involving the 3 sets of variables. It consisted in inferring intra-omic networks with sparse partial correlations and inter-omic networks with regularized canonical correlation analysis and finally combining the obtained omic-specific network in a single global model. The resulting networks were analyzed using node clustering, systematic important node extraction and cluster comparisons. Overall, AT showed both constant and phase-specific biological signatures in response to dietary intervention. AT from women regaining weight displayed growth factors, angiogenesis and proliferation signaling signatures, suggesting unfavorable tissue hyperplasia. By contrast, after LCD a strong positive relationship between AT myristoleic acid (a fatty acid with low AT level) content and de novo lipogenesis mRNAs was found. This relationship was also observed, after WMD, in the group of women that continued to lose weight. This original system biology approach provides novel insight in the AT response to weight control by highlighting the central role of myristoleic acid that may account for the beneficial effects of weight loss. PMID:25590576

Interlocking directorates in Irish companies using a latent space model for bipartite networks

PubMed Central

Friel, Nial; Rastelli, Riccardo; Wyse, Jason; Raftery, Adrian E.

2016-01-01

We analyze the temporal bipartite network of the leading Irish companies and their directors from 2003 to 2013, encompassing the end of the Celtic Tiger boom and the ensuing financial crisis in 2008. We focus on the evolution of company interlocks, whereby a company director simultaneously sits on two or more boards. We develop a statistical model for this dataset by embedding the positions of companies and directors in a latent space. The temporal evolution of the network is modeled through three levels of Markovian dependence: one on the model parameters, one on the companies’ latent positions, and one on the edges themselves. The model is estimated using Bayesian inference. Our analysis reveals that the level of interlocking, as measured by a contraction of the latent space, increased before and during the crisis, reaching a peak in 2009, and has generally stabilized since then. PMID:27247395
Interlocking directorates in Irish companies using a latent space model for bipartite networks.

PubMed

Friel, Nial; Rastelli, Riccardo; Wyse, Jason; Raftery, Adrian E

2016-06-14

We analyze the temporal bipartite network of the leading Irish companies and their directors from 2003 to 2013, encompassing the end of the Celtic Tiger boom and the ensuing financial crisis in 2008. We focus on the evolution of company interlocks, whereby a company director simultaneously sits on two or more boards. We develop a statistical model for this dataset by embedding the positions of companies and directors in a latent space. The temporal evolution of the network is modeled through three levels of Markovian dependence: one on the model parameters, one on the companies' latent positions, and one on the edges themselves. The model is estimated using Bayesian inference. Our analysis reveals that the level of interlocking, as measured by a contraction of the latent space, increased before and during the crisis, reaching a peak in 2009, and has generally stabilized since then.
A stochastic and dynamical view of pluripotency in mouse embryonic stem cells

PubMed Central

Lee, Esther J.

2018-01-01

Pluripotent embryonic stem cells are of paramount importance for biomedical sciences because of their innate ability for self-renewal and differentiation into all major cell lines. The fateful decision to exit or remain in the pluripotent state is regulated by complex genetic regulatory networks. The rapid growth of single-cell sequencing data has greatly stimulated applications of statistical and machine learning methods for inferring topologies of pluripotency regulating genetic networks. The inferred network topologies, however, often only encode Boolean information while remaining silent about the roles of dynamics and molecular stochasticity inherent in gene expression. Herein we develop a framework for systematically extending Boolean-level network topologies into higher resolution models of networks which explicitly account for the promoter architectures and gene state switching dynamics. We show the framework to be useful for disentangling the various contributions that gene switching, external signaling, and network topology make to the global heterogeneity and dynamics of transcription factor populations. We find the pluripotent state of the network to be a steady state which is robust to global variations of gene switching rates which we argue are a good proxy for epigenetic states of individual promoters. The temporal dynamics of exiting the pluripotent state, on the other hand, is significantly influenced by the rates of genetic switching which makes cells more responsive to changes in extracellular signals. PMID:29451874
Machine Learning-Assisted Network Inference Approach to Identify a New Class of Genes that Coordinate the Functionality of Cancer Networks.

PubMed

Ghanat Bari, Mehrab; Ung, Choong Yong; Zhang, Cheng; Zhu, Shizhen; Li, Hu

2017-08-01

Emerging evidence indicates the existence of a new class of cancer genes that act as "signal linkers" coordinating oncogenic signals between mutated and differentially expressed genes. While frequently mutated oncogenes and differentially expressed genes, which we term Class I cancer genes, are readily detected by most analytical tools, the new class of cancer-related genes, i.e., Class II, escape detection because they are neither mutated nor differentially expressed. Given this hypothesis, we developed a Machine Learning-Assisted Network Inference (MALANI) algorithm, which assesses all genes regardless of expression or mutational status in the context of cancer etiology. We used 8807 expression arrays, corresponding to 9 cancer types, to build more than 2 × 10 8 Support Vector Machine (SVM) models for reconstructing a cancer network. We found that ~3% of ~19,000 not differentially expressed genes are Class II cancer gene candidates. Some Class II genes that we found, such as SLC19A1 and ATAD3B, have been recently reported to associate with cancer outcomes. To our knowledge, this is the first study that utilizes both machine learning and network biology approaches to uncover Class II cancer genes in coordinating functionality in cancer networks and will illuminate our understanding of how genes are modulated in a tissue-specific network contribute to tumorigenesis and therapy development.
PPARα siRNA–Treated Expression Profiles Uncover the Causal Sufficiency Network for Compound-Induced Liver Hypertrophy

PubMed Central

Dai, Xudong; Souza, Angus T. De; Dai, Hongyue; Lewis, David L; Lee, Chang-kyu; Spencer, Andy G; Herweijer, Hans; Hagstrom, Jim E; Linsley, Peter S; Bassett, Douglas E; Ulrich, Roger G; He, Yudong D

2007-01-01

Uncovering pathways underlying drug-induced toxicity is a fundamental objective in the field of toxicogenomics. Developing mechanism-based toxicity biomarkers requires the identification of such novel pathways and the order of their sufficiency in causing a phenotypic response. Genome-wide RNA interference (RNAi) phenotypic screening has emerged as an effective tool in unveiling the genes essential for specific cellular functions and biological activities. However, eliciting the relative contribution of and sufficiency relationships among the genes identified remains challenging. In the rodent, the most widely used animal model in preclinical studies, it is unrealistic to exhaustively examine all potential interactions by RNAi screening. Application of existing computational approaches to infer regulatory networks with biological outcomes in the rodent is limited by the requirements for a large number of targeted permutations. Therefore, we developed a two-step relay method that requires only one targeted perturbation for genome-wide de novo pathway discovery. Using expression profiles in response to small interfering RNAs (siRNAs) against the gene for peroxisome proliferator-activated receptor α (Ppara), our method unveiled the potential causal sufficiency order network for liver hypertrophy in the rodent. The validity of the inferred 16 causal transcripts or 15 known genes for PPARα-induced liver hypertrophy is supported by their ability to predict non-PPARα–induced liver hypertrophy with 84% sensitivity and 76% specificity. Simulation shows that the probability of achieving such predictive accuracy without the inferred causal relationship is exceedingly small (p < 0.005). Five of the most sufficient causal genes have been previously disrupted in mouse models; the resulting phenotypic changes in the liver support the inferred causal roles in liver hypertrophy. Our results demonstrate the feasibility of defining pathways mediating drug-induced toxicity from siRNA-treated expression profiles. When combined with phenotypic evaluation, our approach should help to unleash the full potential of siRNAs in systematically unveiling the molecular mechanism of biological events. PMID:17335344
Top-down attention based on object representation and incremental memory for knowledge building and inference.

PubMed

Kim, Bumhwi; Ban, Sang-Woo; Lee, Minho

2013-10-01

Humans can efficiently perceive arbitrary visual objects based on an incremental learning mechanism with selective attention. This paper proposes a new task specific top-down attention model to locate a target object based on its form and color representation along with a bottom-up saliency based on relativity of primitive visual features and some memory modules. In the proposed model top-down bias signals corresponding to the target form and color features are generated, which draw the preferential attention to the desired object by the proposed selective attention model in concomitance with the bottom-up saliency process. The object form and color representation and memory modules have an incremental learning mechanism together with a proper object feature representation scheme. The proposed model includes a Growing Fuzzy Topology Adaptive Resonance Theory (GFTART) network which plays two important roles in object color and form biased attention; one is to incrementally learn and memorize color and form features of various objects, and the other is to generate a top-down bias signal to localize a target object by focusing on the candidate local areas. Moreover, the GFTART network can be utilized for knowledge inference which enables the perception of new unknown objects on the basis of the object form and color features stored in the memory during training. Experimental results show that the proposed model is successful in focusing on the specified target objects, in addition to the incremental representation and memorization of various objects in natural scenes. In addition, the proposed model properly infers new unknown objects based on the form and color features of previously trained objects. Copyright © 2013 Elsevier Ltd. All rights reserved.
Authorship attribution based on Life-Like Network Automata.

PubMed

Machicao, Jeaneth; Corrêa, Edilson A; Miranda, Gisele H B; Amancio, Diego R; Bruno, Odemir M

2018-01-01

The authorship attribution is a problem of considerable practical and technical interest. Several methods have been designed to infer the authorship of disputed documents in multiple contexts. While traditional statistical methods based solely on word counts and related measurements have provided a simple, yet effective solution in particular cases; they are prone to manipulation. Recently, texts have been successfully modeled as networks, where words are represented by nodes linked according to textual similarity measurements. Such models are useful to identify informative topological patterns for the authorship recognition task. However, there is no consensus on which measurements should be used. Thus, we proposed a novel method to characterize text networks, by considering both topological and dynamical aspects of networks. Using concepts and methods from cellular automata theory, we devised a strategy to grasp informative spatio-temporal patterns from this model. Our experiments revealed an outperformance over structural analysis relying only on topological measurements, such as clustering coefficient, betweenness and shortest paths. The optimized results obtained here pave the way for a better characterization of textual networks.
Resolving Structural Variability in Network Models and the Brain

PubMed Central

Klimm, Florian; Bassett, Danielle S.; Carlson, Jean M.; Mucha, Peter J.

2014-01-01

Large-scale white matter pathways crisscrossing the cortex create a complex pattern of connectivity that underlies human cognitive function. Generative mechanisms for this architecture have been difficult to identify in part because little is known in general about mechanistic drivers of structured networks. Here we contrast network properties derived from diffusion spectrum imaging data of the human brain with 13 synthetic network models chosen to probe the roles of physical network embedding and temporal network growth. We characterize both the empirical and synthetic networks using familiar graph metrics, but presented here in a more complete statistical form, as scatter plots and distributions, to reveal the full range of variability of each measure across scales in the network. We focus specifically on the degree distribution, degree assortativity, hierarchy, topological Rentian scaling, and topological fractal scaling—in addition to several summary statistics, including the mean clustering coefficient, the shortest path-length, and the network diameter. The models are investigated in a progressive, branching sequence, aimed at capturing different elements thought to be important in the brain, and range from simple random and regular networks, to models that incorporate specific growth rules and constraints. We find that synthetic models that constrain the network nodes to be physically embedded in anatomical brain regions tend to produce distributions that are most similar to the corresponding measurements for the brain. We also find that network models hardcoded to display one network property (e.g., assortativity) do not in general simultaneously display a second (e.g., hierarchy). This relative independence of network properties suggests that multiple neurobiological mechanisms might be at play in the development of human brain network architecture. Together, the network models that we develop and employ provide a potentially useful starting point for the statistical inference of brain network structure from neuroimaging data. PMID:24675546
Integrating Information in Biological Ontologies and Molecular Networks to Infer Novel Terms

PubMed Central

Li, Le; Yip, Kevin Y.

2016-01-01

Currently most terms and term-term relationships in Gene Ontology (GO) are defined manually, which creates cost, consistency and completeness issues. Recent studies have demonstrated the feasibility of inferring GO automatically from biological networks, which represents an important complementary approach to GO construction. These methods (NeXO and CliXO) are unsupervised, which means 1) they cannot use the information contained in existing GO, 2) the way they integrate biological networks may not optimize the accuracy, and 3) they are not customized to infer the three different sub-ontologies of GO. Here we present a semi-supervised method called Unicorn that extends these previous methods to tackle the three problems. Unicorn uses a sub-tree of an existing GO sub-ontology as training part to learn parameters in integrating multiple networks. Cross-validation results show that Unicorn reliably inferred the left-out parts of each specific GO sub-ontology. In addition, by training Unicorn with an old version of GO together with biological networks, it successfully re-discovered some terms and term-term relationships present only in a new version of GO. Unicorn also successfully inferred some novel terms that were not contained in GO but have biological meanings well-supported by the literature.Availability: Source code of Unicorn is available at http://yiplab.cse.cuhk.edu.hk/unicorn/. PMID:27976738
OWL reasoning framework over big biological knowledge network.

PubMed

Chen, Huajun; Chen, Xi; Gu, Peiqin; Wu, Zhaohui; Yu, Tong

2014-01-01

Recently, huge amounts of data are generated in the domain of biology. Embedded with domain knowledge from different disciplines, the isolated biological resources are implicitly connected. Thus it has shaped a big network of versatile biological knowledge. Faced with such massive, disparate, and interlinked biological data, providing an efficient way to model, integrate, and analyze the big biological network becomes a challenge. In this paper, we present a general OWL (web ontology language) reasoning framework to study the implicit relationships among biological entities. A comprehensive biological ontology across traditional Chinese medicine (TCM) and western medicine (WM) is used to create a conceptual model for the biological network. Then corresponding biological data is integrated into a biological knowledge network as the data model. Based on the conceptual model and data model, a scalable OWL reasoning method is utilized to infer the potential associations between biological entities from the biological network. In our experiment, we focus on the association discovery between TCM and WM. The derived associations are quite useful for biologists to promote the development of novel drugs and TCM modernization. The experimental results show that the system achieves high efficiency, accuracy, scalability, and effectivity.
OWL Reasoning Framework over Big Biological Knowledge Network

PubMed Central

Chen, Huajun; Chen, Xi; Gu, Peiqin; Wu, Zhaohui; Yu, Tong

2014-01-01

Recently, huge amounts of data are generated in the domain of biology. Embedded with domain knowledge from different disciplines, the isolated biological resources are implicitly connected. Thus it has shaped a big network of versatile biological knowledge. Faced with such massive, disparate, and interlinked biological data, providing an efficient way to model, integrate, and analyze the big biological network becomes a challenge. In this paper, we present a general OWL (web ontology language) reasoning framework to study the implicit relationships among biological entities. A comprehensive biological ontology across traditional Chinese medicine (TCM) and western medicine (WM) is used to create a conceptual model for the biological network. Then corresponding biological data is integrated into a biological knowledge network as the data model. Based on the conceptual model and data model, a scalable OWL reasoning method is utilized to infer the potential associations between biological entities from the biological network. In our experiment, we focus on the association discovery between TCM and WM. The derived associations are quite useful for biologists to promote the development of novel drugs and TCM modernization. The experimental results show that the system achieves high efficiency, accuracy, scalability, and effectivity. PMID:24877076
LATENT SPACE MODELS FOR MULTIVIEW NETWORK DATA

PubMed Central

Salter-Townshend, Michael; McCormick, Tyler H.

2018-01-01

Social relationships consist of interactions along multiple dimensions. In social networks, this means that individuals form multiple types of relationships with the same person (e.g., an individual will not trust all of his/her acquaintances). Statistical models for these data require understanding two related types of dependence structure: (i) structure within each relationship type, or network view, and (ii) the association between views. In this paper, we propose a statistical framework that parsimoniously represents dependence between relationship types while also maintaining enough flexibility to allow individuals to serve different roles in different relationship types. Our approach builds on work on latent space models for networks [see, e.g., J. Amer. Statist. Assoc. 97 (2002) 1090–1098]. These models represent the propensity for two individuals to form edges as conditionally independent given the distance between the individuals in an unobserved social space. Our work departs from previous work in this area by representing dependence structure between network views through a multivariate Bernoulli likelihood, providing a representation of between-view association. This approach infers correlations between views not explained by the latent space model. Using our method, we explore 6 multiview network structures across 75 villages in rural southern Karnataka, India [Banerjee et al. (2013)]. PMID:29721127
LATENT SPACE MODELS FOR MULTIVIEW NETWORK DATA.

PubMed

Salter-Townshend, Michael; McCormick, Tyler H

2017-09-01

Social relationships consist of interactions along multiple dimensions. In social networks, this means that individuals form multiple types of relationships with the same person (e.g., an individual will not trust all of his/her acquaintances). Statistical models for these data require understanding two related types of dependence structure: (i) structure within each relationship type, or network view, and (ii) the association between views. In this paper, we propose a statistical framework that parsimoniously represents dependence between relationship types while also maintaining enough flexibility to allow individuals to serve different roles in different relationship types. Our approach builds on work on latent space models for networks [see, e.g., J. Amer. Statist. Assoc. 97 (2002) 1090-1098]. These models represent the propensity for two individuals to form edges as conditionally independent given the distance between the individuals in an unobserved social space. Our work departs from previous work in this area by representing dependence structure between network views through a multivariate Bernoulli likelihood, providing a representation of between-view association. This approach infers correlations between views not explained by the latent space model. Using our method, we explore 6 multiview network structures across 75 villages in rural southern Karnataka, India [Banerjee et al. (2013)].
Deep learning with coherent nanophotonic circuits

NASA Astrophysics Data System (ADS)

Shen, Yichen; Harris, Nicholas C.; Skirlo, Scott; Prabhu, Mihika; Baehr-Jones, Tom; Hochberg, Michael; Sun, Xin; Zhao, Shijie; Larochelle, Hugo; Englund, Dirk; Soljačić, Marin

2017-07-01

Artificial neural networks are computational network models inspired by signal processing in the brain. These models have dramatically improved performance for many machine-learning tasks, including speech and image recognition. However, today's computing hardware is inefficient at implementing neural networks, in large part because much of it was designed for von Neumann computing schemes. Significant effort has been made towards developing electronic architectures tuned to implement artificial neural networks that exhibit improved computational speed and accuracy. Here, we propose a new architecture for a fully optical neural network that, in principle, could offer an enhancement in computational speed and power efficiency over state-of-the-art electronics for conventional inference tasks. We experimentally demonstrate the essential part of the concept using a programmable nanophotonic processor featuring a cascaded array of 56 programmable Mach-Zehnder interferometers in a silicon photonic integrated circuit and show its utility for vowel recognition.
Data-driven forecasting of high-dimensional chaotic systems with long short-term memory networks.

PubMed

Vlachas, Pantelis R; Byeon, Wonmin; Wan, Zhong Y; Sapsis, Themistoklis P; Koumoutsakos, Petros

2018-05-01

We introduce a data-driven forecasting method for high-dimensional chaotic systems using long short-term memory (LSTM) recurrent neural networks. The proposed LSTM neural networks perform inference of high-dimensional dynamical systems in their reduced order space and are shown to be an effective set of nonlinear approximators of their attractor. We demonstrate the forecasting performance of the LSTM and compare it with Gaussian processes (GPs) in time series obtained from the Lorenz 96 system, the Kuramoto-Sivashinsky equation and a prototype climate model. The LSTM networks outperform the GPs in short-term forecasting accuracy in all applications considered. A hybrid architecture, extending the LSTM with a mean stochastic model (MSM-LSTM), is proposed to ensure convergence to the invariant measure. This novel hybrid method is fully data-driven and extends the forecasting capabilities of LSTM networks.
Annealed Importance Sampling for Neural Mass Models

PubMed Central

Penny, Will; Sengupta, Biswa

2016-01-01

Neural Mass Models provide a compact description of the dynamical activity of cell populations in neocortical regions. Moreover, models of regional activity can be connected together into networks, and inferences made about the strength of connections, using M/EEG data and Bayesian inference. To date, however, Bayesian methods have been largely restricted to the Variational Laplace (VL) algorithm which assumes that the posterior distribution is Gaussian and finds model parameters that are only locally optimal. This paper explores the use of Annealed Importance Sampling (AIS) to address these restrictions. We implement AIS using proposals derived from Langevin Monte Carlo (LMC) which uses local gradient and curvature information for efficient exploration of parameter space. In terms of the estimation of Bayes factors, VL and AIS agree about which model is best but report different degrees of belief. Additionally, AIS finds better model parameters and we find evidence of non-Gaussianity in their posterior distribution. PMID:26942606
Learning abstract visual concepts via probabilistic program induction in a Language of Thought.

PubMed

Overlan, Matthew C; Jacobs, Robert A; Piantadosi, Steven T

2017-11-01

The ability to learn abstract concepts is a powerful component of human cognition. It has been argued that variable binding is the key element enabling this ability, but the computational aspects of variable binding remain poorly understood. Here, we address this shortcoming by formalizing the Hierarchical Language of Thought (HLOT) model of rule learning. Given a set of data items, the model uses Bayesian inference to infer a probability distribution over stochastic programs that implement variable binding. Because the model makes use of symbolic variables as well as Bayesian inference and programs with stochastic primitives, it combines many of the advantages of both symbolic and statistical approaches to cognitive modeling. To evaluate the model, we conducted an experiment in which human subjects viewed training items and then judged which test items belong to the same concept as the training items. We found that the HLOT model provides a close match to human generalization patterns, significantly outperforming two variants of the Generalized Context Model, one variant based on string similarity and the other based on visual similarity using features from a deep convolutional neural network. Additional results suggest that variable binding happens automatically, implying that binding operations do not add complexity to peoples' hypothesized rules. Overall, this work demonstrates that a cognitive model combining symbolic variables with Bayesian inference and stochastic program primitives provides a new perspective for understanding people's patterns of generalization. Copyright © 2017 Elsevier B.V. All rights reserved.
Inference on network statistics by restricting to the network space: applications to sexual history data.

PubMed

Goyal, Ravi; De Gruttola, Victor

2018-01-30

Analysis of sexual history data intended to describe sexual networks presents many challenges arising from the fact that most surveys collect information on only a very small fraction of the population of interest. In addition, partners are rarely identified and responses are subject to reporting biases. Typically, each network statistic of interest, such as mean number of sexual partners for men or women, is estimated independently of other network statistics. There is, however, a complex relationship among networks statistics; and knowledge of these relationships can aid in addressing concerns mentioned earlier. We develop a novel method that constrains a posterior predictive distribution of a collection of network statistics in order to leverage the relationships among network statistics in making inference about network properties of interest. The method ensures that inference on network properties is compatible with an actual network. Through extensive simulation studies, we also demonstrate that use of this method can improve estimates in settings where there is uncertainty that arises both from sampling and from systematic reporting bias compared with currently available approaches to estimation. To illustrate the method, we apply it to estimate network statistics using data from the Chicago Health and Social Life Survey. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.
A Hybrid Neuro-Fuzzy Model For Integrating Large Earth-Science Datasets

NASA Astrophysics Data System (ADS)

Porwal, A.; Carranza, J.; Hale, M.

2004-12-01

A GIS-based hybrid neuro-fuzzy approach to integration of large earth-science datasets for mineral prospectivity mapping is described. It implements a Takagi-Sugeno type fuzzy inference system in the framework of a four-layered feed-forward adaptive neural network. Each unique combination of the datasets is considered a feature vector whose components are derived by knowledge-based ordinal encoding of the constituent datasets. A subset of feature vectors with a known output target vector (i.e., unique conditions known to be associated with either a mineralized or a barren location) is used for the training of an adaptive neuro-fuzzy inference system. Training involves iterative adjustment of parameters of the adaptive neuro-fuzzy inference system using a hybrid learning procedure for mapping each training vector to its output target vector with minimum sum of squared error. The trained adaptive neuro-fuzzy inference system is used to process all feature vectors. The output for each feature vector is a value that indicates the extent to which a feature vector belongs to the mineralized class or the barren class. These values are used to generate a prospectivity map. The procedure is demonstrated by an application to regional-scale base metal prospectivity mapping in a study area located in the Aravalli metallogenic province (western India). A comparison of the hybrid neuro-fuzzy approach with pure knowledge-driven fuzzy and pure data-driven neural network approaches indicates that the former offers a superior method for integrating large earth-science datasets for predictive spatial mathematical modelling.
Methods for inferring health-related social networks among coworkers from online communication patterns.

PubMed

Matthews, Luke J; DeWan, Peter; Rula, Elizabeth Y

2013-01-01

Studies of social networks, mapped using self-reported contacts, have demonstrated the strong influence of social connections on the propensity for individuals to adopt or maintain healthy behaviors and on their likelihood to adopt health risks such as obesity. Social network analysis may prove useful for businesses and organizations that wish to improve the health of their populations by identifying key network positions. Health traits have been shown to correlate across friendship ties, but evaluating network effects in large coworker populations presents the challenge of obtaining sufficiently comprehensive network data. The purpose of this study was to evaluate methods for using online communication data to generate comprehensive network maps that reproduce the health-associated properties of an offline social network. In this study, we examined three techniques for inferring social relationships from email traffic data in an employee population using thresholds based on: (1) the absolute number of emails exchanged, (2) logistic regression probability of an offline relationship, and (3) the highest ranked email exchange partners. As a model of the offline social network in the same population, a network map was created using social ties reported in a survey instrument. The email networks were evaluated based on the proportion of survey ties captured, comparisons of common network metrics, and autocorrelation of body mass index (BMI) across social ties. Results demonstrated that logistic regression predicted the greatest proportion of offline social ties, thresholding on number of emails exchanged produced the best match to offline network metrics, and ranked email partners demonstrated the strongest autocorrelation of BMI. Since each method had unique strengths, researchers should choose a method based on the aspects of offline behavior of interest. Ranked email partners may be particularly useful for purposes related to health traits in a social network.

Methods for Inferring Health-Related Social Networks among Coworkers from Online Communication Patterns

PubMed Central

Matthews, Luke J.; DeWan, Peter; Rula, Elizabeth Y.

2013-01-01

Studies of social networks, mapped using self-reported contacts, have demonstrated the strong influence of social connections on the propensity for individuals to adopt or maintain healthy behaviors and on their likelihood to adopt health risks such as obesity. Social network analysis may prove useful for businesses and organizations that wish to improve the health of their populations by identifying key network positions. Health traits have been shown to correlate across friendship ties, but evaluating network effects in large coworker populations presents the challenge of obtaining sufficiently comprehensive network data. The purpose of this study was to evaluate methods for using online communication data to generate comprehensive network maps that reproduce the health-associated properties of an offline social network. In this study, we examined three techniques for inferring social relationships from email traffic data in an employee population using thresholds based on: (1) the absolute number of emails exchanged, (2) logistic regression probability of an offline relationship, and (3) the highest ranked email exchange partners. As a model of the offline social network in the same population, a network map was created using social ties reported in a survey instrument. The email networks were evaluated based on the proportion of survey ties captured, comparisons of common network metrics, and autocorrelation of body mass index (BMI) across social ties. Results demonstrated that logistic regression predicted the greatest proportion of offline social ties, thresholding on number of emails exchanged produced the best match to offline network metrics, and ranked email partners demonstrated the strongest autocorrelation of BMI. Since each method had unique strengths, researchers should choose a method based on the aspects of offline behavior of interest. Ranked email partners may be particularly useful for purposes related to health traits in a social network. PMID:23418436
A novel multilayer model for missing link prediction and future link forecasting in dynamic complex networks

NASA Astrophysics Data System (ADS)

Yasami, Yasser; Safaei, Farshad

2018-02-01

The traditional complex network theory is particularly focused on network models in which all network constituents are dealt with equivalently, while fail to consider the supplementary information related to the dynamic properties of the network interactions. This is a main constraint leading to incorrect descriptions of some real-world phenomena or incomplete capturing the details of certain real-life problems. To cope with the problem, this paper addresses the multilayer aspects of dynamic complex networks by analyzing the properties of intrinsically multilayered co-authorship networks, DBLP and Astro Physics, and presenting a novel multilayer model of dynamic complex networks. The model examines the layers evolution (layers birth/death process and lifetime) throughout the network evolution. Particularly, this paper models the evolution of each node's membership in different layers by an Infinite Factorial Hidden Markov Model considering feature cascade, and thereby formulates the link generation process for intra-layer and inter-layer links. Although adjacency matrixes are useful to describe the traditional single-layer networks, such a representation is not sufficient to describe and analyze the multilayer dynamic networks. This paper also extends a generalized mathematical infrastructure to address the problems issued by multilayer complex networks. The model inference is performed using some Markov Chain Monte Carlo sampling strategies, given synthetic and real complex networks data. Experimental results indicate a tremendous improvement in the performance of the proposed multilayer model in terms of sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios, F1-score, Matthews correlation coefficient, and accuracy for two important applications of missing link prediction and future link forecasting. The experimental results also indicate the strong predictivepower of the proposed model for the application of cascade prediction in terms of accuracy.
Decision generation tools and Bayesian inference

NASA Astrophysics Data System (ADS)

Jannson, Tomasz; Wang, Wenjian; Forrester, Thomas; Kostrzewski, Andrew; Veeris, Christian; Nielsen, Thomas

2014-05-01

Digital Decision Generation (DDG) tools are important software sub-systems of Command and Control (C2) systems and technologies. In this paper, we present a special type of DDGs based on Bayesian Inference, related to adverse (hostile) networks, including such important applications as terrorism-related networks and organized crime ones.
Modeling Array Stations in SIG-VISA

NASA Astrophysics Data System (ADS)

Ding, N.; Moore, D.; Russell, S.

2013-12-01

We add support for array stations to SIG-VISA, a system for nuclear monitoring using probabilistic inference on seismic signals. Array stations comprise a large portion of the IMS network; they can provide increased sensitivity and more accurate directional information compared to single-component stations. Our existing model assumed that signals were independent at each station, which is false when lots of stations are close together, as in an array. The new model removes that assumption by jointly modeling signals across array elements. This is done by extending our existing Gaussian process (GP) regression models, also known as kriging, from a 3-dimensional single-component space of events to a 6-dimensional space of station-event pairs. For each array and each event attribute (including coda decay, coda height, amplitude transfer and travel time), we model the joint distribution across array elements using a Gaussian process that learns the correlation lengthscale across the array, thereby incorporating information of array stations into the probabilistic inference framework. To evaluate the effectiveness of our model, we perform ';probabilistic beamforming' on new events using our GP model, i.e., we compute the event azimuth having highest posterior probability under the model, conditioned on the signals at array elements. We compare the results from our probabilistic inference model to the beamforming currently performed by IMS station processing.
A conceptual model for site-level ecology of the giant gartersnake (Thamnophis gigas) in the Sacramento Valley, California

USGS Publications Warehouse

Halstead, Brian J.; Wylie, Glenn D.; Casazza, Michael L.; Hansen, Eric C.; Scherer, Rick D.; Patterson, Laura C.

2015-08-14

Bayesian networks further provide a clear visual display of the model that facilitates understanding among various stakeholders (Marcot and others, 2001; Uusitalo , 2007). Empirical data and expert judgment can be combined, as continuous or categorical variables, to update knowledge about the system (Marcot and others, 2001; Uusitalo , 2007). Importantly, Bayesian network models allow inference from causes to consequences, but also from consequences to causes, so that data can inform the states of nodes (values of different random variables) in either direction (Marcot and others, 2001; Uusitalo , 2007). Because they can incorporate both decision nodes that represent management actions and utility nodes that quantify the costs and benefits of outcomes, Bayesian networks are ideally suited to risk analysis and adaptive management (Nyberg and others, 2006; Howes and others, 2010). Thus, Bayesian network models are useful in situations where empirical data are not available, such as questions concerning the responses of giant gartersnakes to management.
Identification of Patient Zero in Static and Temporal Networks: Robustness and Limitations

NASA Astrophysics Data System (ADS)

Antulov-Fantulin, Nino; Lančić, Alen; Šmuc, Tomislav; Štefančić, Hrvoje; Šikić, Mile

2015-06-01

Detection of patient zero can give new insights to epidemiologists about the nature of first transmissions into a population. In this Letter, we study the statistical inference problem of detecting the source of epidemics from a snapshot of spreading on an arbitrary network structure. By using exact analytic calculations and Monte Carlo estimators, we demonstrate the detectability limits for the susceptible-infected-recovered model, which primarily depend on the spreading process characteristics. Finally, we demonstrate the applicability of the approach in a case of a simulated sexually transmitted infection spreading over an empirical temporal network of sexual interactions.
Genexpi: a toolset for identifying regulons and validating gene regulatory networks using time-course expression data.

PubMed

Modrák, Martin; Vohradský, Jiří

2018-04-13

Identifying regulons of sigma factors is a vital subtask of gene network inference. Integrating multiple sources of data is essential for correct identification of regulons and complete gene regulatory networks. Time series of expression data measured with microarrays or RNA-seq combined with static binding experiments (e.g., ChIP-seq) or literature mining may be used for inference of sigma factor regulatory networks. We introduce Genexpi: a tool to identify sigma factors by combining candidates obtained from ChIP experiments or literature mining with time-course gene expression data. While Genexpi can be used to infer other types of regulatory interactions, it was designed and validated on real biological data from bacterial regulons. In this paper, we put primary focus on CyGenexpi: a plugin integrating Genexpi with the Cytoscape software for ease of use. As a part of this effort, a plugin for handling time series data in Cytoscape called CyDataseries has been developed and made available. Genexpi is also available as a standalone command line tool and an R package. Genexpi is a useful part of gene network inference toolbox. It provides meaningful information about the composition of regulons and delivers biologically interpretable results.
A Network Biology Approach Identifies Molecular Cross-Talk between Normal Prostate Epithelial and Prostate Carcinoma Cells

PubMed Central

Trevino, Victor; Cassese, Alberto; Nagy, Zsuzsanna; Zhuang, Xiaodong; Herbert, John; Antzack, Philipp; Clarke, Kim; Davies, Nicholas; Rahman, Ayesha; Campbell, Moray J.; Bicknell, Roy; Vannucci, Marina; Falciani, Francesco

2016-01-01

Abstract The advent of functional genomics has enabled the genome-wide characterization of the molecular state of cells and tissues, virtually at every level of biological organization. The difficulty in organizing and mining this unprecedented amount of information has stimulated the development of computational methods designed to infer the underlying structure of regulatory networks from observational data. These important developments had a profound impact in biological sciences since they triggered the development of a novel data-driven investigative approach. In cancer research, this strategy has been particularly successful. It has contributed to the identification of novel biomarkers, to a better characterization of disease heterogeneity and to a more in depth understanding of cancer pathophysiology. However, so far these approaches have not explicitly addressed the challenge of identifying networks representing the interaction of different cell types in a complex tissue. Since these interactions represent an essential part of the biology of both diseased and healthy tissues, it is of paramount importance that this challenge is addressed. Here we report the definition of a network reverse engineering strategy designed to infer directional signals linking adjacent cell types within a complex tissue. The application of this inference strategy to prostate cancer genome-wide expression profiling data validated the approach and revealed that normal epithelial cells exert an anti-tumour activity on prostate carcinoma cells. Moreover, by using a Bayesian hierarchical model integrating genetics and gene expression data and combining this with survival analysis, we show that the expression of putative cell communication genes related to focal adhesion and secretion is affected by epistatic gene copy number variation and it is predictive of patient survival. Ultimately, this study represents a generalizable approach to the challenge of deciphering cell communication networks in a wide spectrum of biological systems. PMID:27124473
A Network Biology Approach Identifies Molecular Cross-Talk between Normal Prostate Epithelial and Prostate Carcinoma Cells.

PubMed

Trevino, Victor; Cassese, Alberto; Nagy, Zsuzsanna; Zhuang, Xiaodong; Herbert, John; Antczak, Philipp; Clarke, Kim; Davies, Nicholas; Rahman, Ayesha; Campbell, Moray J; Guindani, Michele; Bicknell, Roy; Vannucci, Marina; Falciani, Francesco

2016-04-01

The advent of functional genomics has enabled the genome-wide characterization of the molecular state of cells and tissues, virtually at every level of biological organization. The difficulty in organizing and mining this unprecedented amount of information has stimulated the development of computational methods designed to infer the underlying structure of regulatory networks from observational data. These important developments had a profound impact in biological sciences since they triggered the development of a novel data-driven investigative approach. In cancer research, this strategy has been particularly successful. It has contributed to the identification of novel biomarkers, to a better characterization of disease heterogeneity and to a more in depth understanding of cancer pathophysiology. However, so far these approaches have not explicitly addressed the challenge of identifying networks representing the interaction of different cell types in a complex tissue. Since these interactions represent an essential part of the biology of both diseased and healthy tissues, it is of paramount importance that this challenge is addressed. Here we report the definition of a network reverse engineering strategy designed to infer directional signals linking adjacent cell types within a complex tissue. The application of this inference strategy to prostate cancer genome-wide expression profiling data validated the approach and revealed that normal epithelial cells exert an anti-tumour activity on prostate carcinoma cells. Moreover, by using a Bayesian hierarchical model integrating genetics and gene expression data and combining this with survival analysis, we show that the expression of putative cell communication genes related to focal adhesion and secretion is affected by epistatic gene copy number variation and it is predictive of patient survival. Ultimately, this study represents a generalizable approach to the challenge of deciphering cell communication networks in a wide spectrum of biological systems.
A Method for Using Player Tracking Data in Basketball to Learn Player Skills and Predict Team Performance.

PubMed

Skinner, Brian; Guy, Stephen J

2015-01-01

Player tracking data represents a revolutionary new data source for basketball analysis, in which essentially every aspect of a player's performance is tracked and can be analyzed numerically. We suggest a way by which this data set, when coupled with a network-style model of the offense that relates players' skills to the team's success at running different plays, can be used to automatically learn players' skills and predict the performance of untested 5-man lineups in a way that accounts for the interaction between players' respective skill sets. After developing a general analysis procedure, we present as an example a specific implementation of our method using a simplified network model. While player tracking data is not yet available in the public domain, we evaluate our model using simulated data and show that player skills can be accurately inferred by a simple statistical inference scheme. Finally, we use the model to analyze games from the 2011 playoff series between the Memphis Grizzlies and the Oklahoma City Thunder and we show that, even with a very limited data set, the model can consistently describe a player's interactions with a given lineup based only on his performance with a different lineup.
A Method for Using Player Tracking Data in Basketball to Learn Player Skills and Predict Team Performance

PubMed Central

Skinner, Brian; Guy, Stephen J.

2015-01-01

Player tracking data represents a revolutionary new data source for basketball analysis, in which essentially every aspect of a player’s performance is tracked and can be analyzed numerically. We suggest a way by which this data set, when coupled with a network-style model of the offense that relates players’ skills to the team’s success at running different plays, can be used to automatically learn players’ skills and predict the performance of untested 5-man lineups in a way that accounts for the interaction between players’ respective skill sets. After developing a general analysis procedure, we present as an example a specific implementation of our method using a simplified network model. While player tracking data is not yet available in the public domain, we evaluate our model using simulated data and show that player skills can be accurately inferred by a simple statistical inference scheme. Finally, we use the model to analyze games from the 2011 playoff series between the Memphis Grizzlies and the Oklahoma City Thunder and we show that, even with a very limited data set, the model can consistently describe a player’s interactions with a given lineup based only on his performance with a different lineup. PMID:26351846
Improved representation of situational awareness within a dismounted small combat unit constructive simulation

NASA Astrophysics Data System (ADS)

Lee, K. David; Colony, Mike

2011-06-01

Modeling and simulation has been established as a cost-effective means of supporting the development of requirements, exploring doctrinal alternatives, assessing system performance, and performing design trade-off analysis. The Army's constructive simulation for the evaluation of equipment effectiveness in small combat unit operations is currently limited to representation of situation awareness without inclusion of the many uncertainties associated with real world combat environments. The goal of this research is to provide an ability to model situation awareness and decision process uncertainties in order to improve evaluation of the impact of battlefield equipment on ground soldier and small combat unit decision processes. Our Army Probabilistic Inference and Decision Engine (Army-PRIDE) system provides this required uncertainty modeling through the application of two critical techniques that allow Bayesian network technology to be applied to real-time applications. (Object-Oriented Bayesian Network methodology and Object-Oriented Inference technique). In this research, we implement decision process and situation awareness models for a reference scenario using Army-PRIDE and demonstrate its ability to model a variety of uncertainty elements, including: confidence of source, information completeness, and information loss. We also demonstrate that Army-PRIDE improves the realism of the current constructive simulation's decision processes through Monte Carlo simulation.
Prediction of Tensile Strength of Friction Stir Weld Joints with Adaptive Neuro-Fuzzy Inference System (ANFIS) and Neural Network

NASA Technical Reports Server (NTRS)

Dewan, Mohammad W.; Huggett, Daniel J.; Liao, T. Warren; Wahab, Muhammad A.; Okeil, Ayman M.

2015-01-01

Friction-stir-welding (FSW) is a solid-state joining process where joint properties are dependent on welding process parameters. In the current study three critical process parameters including spindle speed (??), plunge force (????), and welding speed (??) are considered key factors in the determination of ultimate tensile strength (UTS) of welded aluminum alloy joints. A total of 73 weld schedules were welded and tensile properties were subsequently obtained experimentally. It is observed that all three process parameters have direct influence on UTS of the welded joints. Utilizing experimental data, an optimized adaptive neuro-fuzzy inference system (ANFIS) model has been developed to predict UTS of FSW joints. A total of 1200 models were developed by varying the number of membership functions (MFs), type of MFs, and combination of four input variables (??,??,????,??????) utilizing a MATLAB platform. Note EFI denotes an empirical force index derived from the three process parameters. For comparison, optimized artificial neural network (ANN) models were also developed to predict UTS from FSW process parameters. By comparing ANFIS and ANN predicted results, it was found that optimized ANFIS models provide better results than ANN. This newly developed best ANFIS model could be utilized for prediction of UTS of FSW joints.
An ANFIS-based on B2C electronic commerce transaction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Juan, E-mail: linjuanliucaihong@qq.com; Liu, Chenlian, E-mail: chenglian.liu@gmail.com; Guo, Yongning, E-mail: guoyn@163.com

2014-10-06

The purpose of this study is to use an adaptive-network-based fuzzy inference system to model a fuzzy logic-based system (FIS) for supporting decision-making process in B2C electronic commerce transaction. Firstly we introduce FIS in B2C electronic commerce transaction and ANFIS. Then we use ANFIS to model FIS with different membership functions(MF). Lastly we give a conclusion.
An ANFIS-based on B2C electronic commerce transaction

NASA Astrophysics Data System (ADS)

Lin, Juan; Liu, Chenlian; Guo, Yongning

2014-10-01

The purpose of this study is to use an adaptive-network-based fuzzy inference system to model a fuzzy logic-based system (FIS) for supporting decision-making process in B2C electronic commerce transaction. Firstly we introduce FIS in B2C electronic commerce transaction and ANFIS. Then we use ANFIS to model FIS with different membership functions(MF). Lastly we give a conclusion.
Life's attractors : understanding developmental systems through reverse engineering and in silico evolution.

PubMed

Jaeger, Johannes; Crombach, Anton

2012-01-01

We propose an approach to evolutionary systems biology which is based on reverse engineering of gene regulatory networks and in silico evolutionary simulations. We infer regulatory parameters for gene networks by fitting computational models to quantitative expression data. This allows us to characterize the regulatory structure and dynamical repertoire of evolving gene regulatory networks with a reasonable amount of experimental and computational effort. We use the resulting network models to identify those regulatory interactions that are conserved, and those that have diverged between different species. Moreover, we use the models obtained by data fitting as starting points for simulations of evolutionary transitions between species. These simulations enable us to investigate whether such transitions are random, or whether they show stereotypical series of regulatory changes which depend on the structure and dynamical repertoire of an evolving network. Finally, we present a case study-the gap gene network in dipterans (flies, midges, and mosquitoes)-to illustrate the practical application of the proposed methodology, and to highlight the kind of biological insights that can be gained by this approach.
Markov Task Network: A Framework for Service Composition under Uncertainty in Cyber-Physical Systems.

PubMed

Mohammed, Abdul-Wahid; Xu, Yang; Hu, Haixiao; Agyemang, Brighter

2016-09-21

In novel collaborative systems, cooperative entities collaborate services to achieve local and global objectives. With the growing pervasiveness of cyber-physical systems, however, such collaboration is hampered by differences in the operations of the cyber and physical objects, and the need for the dynamic formation of collaborative functionality given high-level system goals has become practical. In this paper, we propose a cross-layer automation and management model for cyber-physical systems. This models the dynamic formation of collaborative services pursuing laid-down system goals as an ontology-oriented hierarchical task network. Ontological intelligence provides the semantic technology of this model, and through semantic reasoning, primitive tasks can be dynamically composed from high-level system goals. In dealing with uncertainty, we further propose a novel bridge between hierarchical task networks and Markov logic networks, called the Markov task network. This leverages the efficient inference algorithms of Markov logic networks to reduce both computational and inferential loads in task decomposition. From the results of our experiments, high-precision service composition under uncertainty can be achieved using this approach.
Harnessing Diversity towards the Reconstructing of Large Scale Gene Regulatory Networks

PubMed Central

Yamanaka, Ryota; Kitano, Hiroaki

2013-01-01

Elucidating gene regulatory network (GRN) from large scale experimental data remains a central challenge in systems biology. Recently, numerous techniques, particularly consensus driven approaches combining different algorithms, have become a potentially promising strategy to infer accurate GRNs. Here, we develop a novel consensus inference algorithm, TopkNet that can integrate multiple algorithms to infer GRNs. Comprehensive performance benchmarking on a cloud computing framework demonstrated that (i) a simple strategy to combine many algorithms does not always lead to performance improvement compared to the cost of consensus and (ii) TopkNet integrating only high-performance algorithms provide significant performance improvement compared to the best individual algorithms and community prediction. These results suggest that a priori determination of high-performance algorithms is a key to reconstruct an unknown regulatory network. Similarity among gene-expression datasets can be useful to determine potential optimal algorithms for reconstruction of unknown regulatory networks, i.e., if expression-data associated with known regulatory network is similar to that with unknown regulatory network, optimal algorithms determined for the known regulatory network can be repurposed to infer the unknown regulatory network. Based on this observation, we developed a quantitative measure of similarity among gene-expression datasets and demonstrated that, if similarity between the two expression datasets is high, TopkNet integrating algorithms that are optimal for known dataset perform well on the unknown dataset. The consensus framework, TopkNet, together with the similarity measure proposed in this study provides a powerful strategy towards harnessing the wisdom of the crowds in reconstruction of unknown regulatory networks. PMID:24278007
The noisy voter model on complex networks.

PubMed

Carro, Adrián; Toral, Raúl; San Miguel, Maxi

2016-04-20

We propose a new analytical method to study stochastic, binary-state models on complex networks. Moving beyond the usual mean-field theories, this alternative approach is based on the introduction of an annealed approximation for uncorrelated networks, allowing to deal with the network structure as parametric heterogeneity. As an illustration, we study the noisy voter model, a modification of the original voter model including random changes of state. The proposed method is able to unfold the dependence of the model not only on the mean degree (the mean-field prediction) but also on more complex averages over the degree distribution. In particular, we find that the degree heterogeneity--variance of the underlying degree distribution--has a strong influence on the location of the critical point of a noise-induced, finite-size transition occurring in the model, on the local ordering of the system, and on the functional form of its temporal correlations. Finally, we show how this latter point opens the possibility of inferring the degree heterogeneity of the underlying network by observing only the aggregate behavior of the system as a whole, an issue of interest for systems where only macroscopic, population level variables can be measured.
Comparative Analysis of Soft Computing Models in Prediction of Bending Rigidity of Cotton Woven Fabrics

NASA Astrophysics Data System (ADS)

Guruprasad, R.; Behera, B. K.

2015-10-01

Quantitative prediction of fabric mechanical properties is an essential requirement for design engineering of textile and apparel products. In this work, the possibility of prediction of bending rigidity of cotton woven fabrics has been explored with the application of Artificial Neural Network (ANN) and two hybrid methodologies, namely Neuro-genetic modeling and Adaptive Neuro-Fuzzy Inference System (ANFIS) modeling. For this purpose, a set of cotton woven grey fabrics was desized, scoured and relaxed. The fabrics were then conditioned and tested for bending properties. With the database thus created, a neural network model was first developed using back propagation as the learning algorithm. The second model was developed by applying a hybrid learning strategy, in which genetic algorithm was first used as a learning algorithm to optimize the number of neurons and connection weights of the neural network. The Genetic algorithm optimized network structure was further allowed to learn using back propagation algorithm. In the third model, an ANFIS modeling approach was attempted to map the input-output data. The prediction performances of the models were compared and a sensitivity analysis was reported. The results show that the prediction by neuro-genetic and ANFIS models were better in comparison with that of back propagation neural network model.

Inferring Adolescent Social Networks Using Partial Ego-Network Substance Use Data

DTIC Science & Technology

2008-05-15

initiation among West Coast youth from age 5 to 23.” Preventive Medicine 44. Ellickson, Phyllis L. and Robert M. Bell. 1990. “Drug prevention in junior high...21:615–632. Jessor, Richard and Shirley L. Jessor. 1978. “Theory testing in longitudinal research on Marihuana use.” In Longitudinal Research on Drug...Science and Medicine 44:1861–1869. Mollison, Denis, Valerie Isham, and Bryan Grenfell. 1994. “Epidemics: models and data.” Journal of the Royal Statistics
Investigating Cell Criticality

NASA Astrophysics Data System (ADS)

Serra, R.; Villani, M.; Damiani, C.; Graudenzi, A.; Ingrami, P.; Colacci, A.

Random Boolean networks provide a way to give a precise meaning to the notion that living beings are in a critical state. Some phenomena which are observed in real biological systems (distribution of "avalanches" in gene knock-out experiments) can be modeled using random Boolean networks, and the results can be analytically proven to depend upon the Derrida parameter, which also determines whether the network is critical. By comparing observed and simulated data one can then draw inferences about the criticality of biological cells, although with some care because of the limited number of experimental observations. The relationship between the criticality of a single network and that of a set of interacting networks, which simulate a tissue or a bacterial colony, is also analyzed by computer simulations.
Metabolic PathFinding: inferring relevant pathways in biochemical networks.

PubMed

Croes, Didier; Couche, Fabian; Wodak, Shoshana J; van Helden, Jacques

2005-07-01

Our knowledge of metabolism can be represented as a network comprising several thousands of nodes (compounds and reactions). Several groups applied graph theory to analyse the topological properties of this network and to infer metabolic pathways by path finding. This is, however, not straightforward, with a major problem caused by traversing irrelevant shortcuts through highly connected nodes, which correspond to pool metabolites and co-factors (e.g. H2O, NADP and H+). In this study, we present a web server implementing two simple approaches, which circumvent this problem, thereby improving the relevance of the inferred pathways. In the simplest approach, the shortest path is computed, while filtering out the selection of highly connected compounds. In the second approach, the shortest path is computed on the weighted metabolic graph where each compound is assigned a weight equal to its connectivity in the network. This approach significantly increases the accuracy of the inferred pathways, enabling the correct inference of relatively long pathways (e.g. with as many as eight intermediate reactions). Available options include the calculation of the k-shortest paths between two specified seed nodes (either compounds or reactions). Multiple requests can be submitted in a queue. Results are returned by email, in textual as well as graphical formats (available in http://www.scmbb.ulb.ac.be/pathfinding/).
INfORM: Inference of NetwOrk Response Modules.

PubMed

Marwah, Veer Singh; Kinaret, Pia Anneli Sofia; Serra, Angela; Scala, Giovanni; Lauerma, Antti; Fortino, Vittorio; Greco, Dario

2018-06-15

Detecting and interpreting responsive modules from gene expression data by using network-based approaches is a common but laborious task. It often requires the application of several computational methods implemented in different software packages, forcing biologists to compile complex analytical pipelines. Here we introduce INfORM (Inference of NetwOrk Response Modules), an R shiny application that enables non-expert users to detect, evaluate and select gene modules with high statistical and biological significance. INfORM is a comprehensive tool for the identification of biologically meaningful response modules from consensus gene networks inferred by using multiple algorithms. It is accessible through an intuitive graphical user interface allowing for a level of abstraction from the computational steps. INfORM is freely available for academic use at https://github.com/Greco-Lab/INfORM. Supplementary data are available at Bioinformatics online.
Deep convolutional neural network for prostate MR segmentation

NASA Astrophysics Data System (ADS)

Tian, Zhiqiang; Liu, Lizhi; Fei, Baowei

2017-03-01

Automatic segmentation of the prostate in magnetic resonance imaging (MRI) has many applications in prostate cancer diagnosis and therapy. We propose a deep fully convolutional neural network (CNN) to segment the prostate automatically. Our deep CNN model is trained end-to-end in a single learning stage based on prostate MR images and the corresponding ground truths, and learns to make inference for pixel-wise segmentation. Experiments were performed on our in-house data set, which contains prostate MR images of 20 patients. The proposed CNN model obtained a mean Dice similarity coefficient of 85.3%+/-3.2% as compared to the manual segmentation. Experimental results show that our deep CNN model could yield satisfactory segmentation of the prostate.
Order priors for Bayesian network discovery with an application to malware phylogeny

DOE PAGES

Oyen, Diane; Anderson, Blake; Sentz, Kari; ...

2017-09-15

Here, Bayesian networks have been used extensively to model and discover dependency relationships among sets of random variables. We learn Bayesian network structure with a combination of human knowledge about the partial ordering of variables and statistical inference of conditional dependencies from observed data. Our approach leverages complementary information from human knowledge and inference from observed data to produce networks that reflect human beliefs about the system as well as to fit the observed data. Applying prior beliefs about partial orderings of variables is an approach distinctly different from existing methods that incorporate prior beliefs about direct dependencies (or edges)more » in a Bayesian network. We provide an efficient implementation of the partial-order prior in a Bayesian structure discovery learning algorithm, as well as an edge prior, showing that both priors meet the local modularity requirement necessary for an efficient Bayesian discovery algorithm. In benchmark studies, the partial-order prior improves the accuracy of Bayesian network structure learning as well as the edge prior, even though order priors are more general. Our primary motivation is in characterizing the evolution of families of malware to aid cyber security analysts. For the problem of malware phylogeny discovery, we find that our algorithm, compared to existing malware phylogeny algorithms, more accurately discovers true dependencies that are missed by other algorithms.« less
Order priors for Bayesian network discovery with an application to malware phylogeny

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oyen, Diane; Anderson, Blake; Sentz, Kari

Here, Bayesian networks have been used extensively to model and discover dependency relationships among sets of random variables. We learn Bayesian network structure with a combination of human knowledge about the partial ordering of variables and statistical inference of conditional dependencies from observed data. Our approach leverages complementary information from human knowledge and inference from observed data to produce networks that reflect human beliefs about the system as well as to fit the observed data. Applying prior beliefs about partial orderings of variables is an approach distinctly different from existing methods that incorporate prior beliefs about direct dependencies (or edges)more » in a Bayesian network. We provide an efficient implementation of the partial-order prior in a Bayesian structure discovery learning algorithm, as well as an edge prior, showing that both priors meet the local modularity requirement necessary for an efficient Bayesian discovery algorithm. In benchmark studies, the partial-order prior improves the accuracy of Bayesian network structure learning as well as the edge prior, even though order priors are more general. Our primary motivation is in characterizing the evolution of families of malware to aid cyber security analysts. For the problem of malware phylogeny discovery, we find that our algorithm, compared to existing malware phylogeny algorithms, more accurately discovers true dependencies that are missed by other algorithms.« less
Hybrid computing using a neural network with dynamic external memory.

PubMed

Graves, Alex; Wayne, Greg; Reynolds, Malcolm; Harley, Tim; Danihelka, Ivo; Grabska-Barwińska, Agnieszka; Colmenarejo, Sergio Gómez; Grefenstette, Edward; Ramalho, Tiago; Agapiou, John; Badia, Adrià Puigdomènech; Hermann, Karl Moritz; Zwols, Yori; Ostrovski, Georg; Cain, Adam; King, Helen; Summerfield, Christopher; Blunsom, Phil; Kavukcuoglu, Koray; Hassabis, Demis

2016-10-27

Artificial neural networks are remarkably adept at sensory processing, sequence learning and reinforcement learning, but are limited in their ability to represent variables and data structures and to store data over long timescales, owing to the lack of an external memory. Here we introduce a machine learning model called a differentiable neural computer (DNC), which consists of a neural network that can read from and write to an external memory matrix, analogous to the random-access memory in a conventional computer. Like a conventional computer, it can use its memory to represent and manipulate complex data structures, but, like a neural network, it can learn to do so from data. When trained with supervised learning, we demonstrate that a DNC can successfully answer synthetic questions designed to emulate reasoning and inference problems in natural language. We show that it can learn tasks such as finding the shortest path between specified points and inferring the missing links in randomly generated graphs, and then generalize these tasks to specific graphs such as transport networks and family trees. When trained with reinforcement learning, a DNC can complete a moving blocks puzzle in which changing goals are specified by sequences of symbols. Taken together, our results demonstrate that DNCs have the capacity to solve complex, structured tasks that are inaccessible to neural networks without external read-write memory.
Modeling the Evolution of Beliefs Using an Attentional Focus Mechanism

PubMed Central

Marković, Dimitrije; Gläscher, Jan; Bossaerts, Peter; O’Doherty, John; Kiebel, Stefan J.

2015-01-01

For making decisions in everyday life we often have first to infer the set of environmental features that are relevant for the current task. Here we investigated the computational mechanisms underlying the evolution of beliefs about the relevance of environmental features in a dynamical and noisy environment. For this purpose we designed a probabilistic Wisconsin card sorting task (WCST) with belief solicitation, in which subjects were presented with stimuli composed of multiple visual features. At each moment in time a particular feature was relevant for obtaining reward, and participants had to infer which feature was relevant and report their beliefs accordingly. To test the hypothesis that attentional focus modulates the belief update process, we derived and fitted several probabilistic and non-probabilistic behavioral models, which either incorporate a dynamical model of attentional focus, in the form of a hierarchical winner-take-all neuronal network, or a diffusive model, without attention-like features. We used Bayesian model selection to identify the most likely generative model of subjects’ behavior and found that attention-like features in the behavioral model are essential for explaining subjects’ responses. Furthermore, we demonstrate a method for integrating both connectionist and Bayesian models of decision making within a single framework that allowed us to infer hidden belief processes of human subjects. PMID:26495984
Estimating regional CO2 and CH4 fluxes using GOSAT XCO2 and XCH4 observations

NASA Astrophysics Data System (ADS)

Fraser, A. C.; Palmer, P. I.; Feng, L.; Parker, R.; Boesch, H.; Cogan, A. J.

2012-12-01

We infer regional monthly surface flux estimates for CO2 and CH4, June 2009-December 2010, from proxy dry-air column-averaged mole fractions of CO2 and CH4 from the Greenhouse gases Observing SATellite (GOSAT) using an ensemble Kalman Filter combined with the GEOS-Chem chemistry transport model. We compare these flux estimates with estimates inferred from in situ surface mole fraction measurements and from combining in situ and GOSAT measurements in order to quantify the added value of GOSAT data above the conventional surface measurement network. We find that the error reduction, a measure of how much the posterior fluxes are being informed by the assimilated data, at least doubles when GOSAT measurements are used versus the surface only inversions, with the exception of regions that are well covered by the surface network at the spatial and temporal resolution of our flux estimation calculation. We have incorporated a new online bias correction scheme to account for GOSAT biases. We report global and regional flux estimates inferred from GOSAT and/or in situ measurements. While the global posterior fluxes from GOSAT and in situ measurements agree, we find significant differences in the regional fluxes, particularly over the tropics. We evaluate the posterior fluxes by comparing them against independent surface mole fraction, column, and aircraft measurements using the GEOS-Chem model as an intermediary.
Example of a Bayes network of relations among visual features

NASA Astrophysics Data System (ADS)

Agosta, John M.

1991-10-01

Bayes probability networks, also termed `influence diagrams,' promise to be a versatile, rigorous, and expressive uncertainty reasoning tool. This paper presents an example of how a Bayes network can express constraints among visual hypotheses. An example is presented of a model composed of cylindric primitives, inferred from a line drawing of a plumbing fixture. Conflict between interpretations of candidate cylinders is expressed by two parameters, one for the presence and one for the absence of visual evidence of their intersection. It is shown how `partial exclusion' relations are so generated and how they determine the degree of competition among the set of hypotheses. Solving this network obtains the assemblies of cylinders most likely to form an object.
Protein Inference from the Integration of Tandem MS Data and Interactome Networks.

PubMed

Zhong, Jiancheng; Wang, Jianxing; Ding, Xiaojun; Zhang, Zhen; Li, Min; Wu, Fang-Xiang; Pan, Yi

2017-01-01

Since proteins are digested into a mixture of peptides in the preprocessing step of tandem mass spectrometry (MS), it is difficult to determine which specific protein a shared peptide belongs to. In recent studies, besides tandem MS data and peptide identification information, some other information is exploited to infer proteins. Different from the methods which first use only tandem MS data to infer proteins and then use network information to refine them, this study proposes a protein inference method named TMSIN, which uses interactome networks directly. As two interacting proteins should co-exist, it is reasonable to assume that if one of the interacting proteins is confidently inferred in a sample, its interacting partners should have a high probability in the same sample, too. Therefore, we can use the neighborhood information of a protein in an interactome network to adjust the probability that the shared peptide belongs to the protein. In TMSIN, a multi-weighted graph is constructed by incorporating the bipartite graph with interactome network information, where the bipartite graph is built with the peptide identification information. Based on multi-weighted graphs, TMSIN adopts an iterative workflow to infer proteins. At each iterative step, the probability that a shared peptide belongs to a specific protein is calculated by using the Bayes' law based on the neighbor protein support scores of each protein which are mapped by the shared peptides. We carried out experiments on yeast data and human data to evaluate the performance of TMSIN in terms of ROC, q-value, and accuracy. The experimental results show that AUC scores yielded by TMSIN are 0.742 and 0.874 in yeast dataset and human dataset, respectively, and TMSIN yields the maximum number of true positives when q-value less than or equal to 0.05. The overlap analysis shows that TMSIN is an effective complementary approach for protein inference.
Personalized microbial network inference via co-regularized spectral clustering.

PubMed

Imangaliyev, Sultan; Keijser, Bart; Crielaard, Wim; Tsivtsivadze, Evgeni

2015-07-15

We use Human Microbiome Project (HMP) cohort (Peterson et al., 2009) to infer personalized oral microbial networks of healthy individuals. To determine clustering of individuals with similar microbial profiles, co-regularized spectral clustering algorithm is applied to the dataset. For each cluster we discovered, we compute co-occurrence relationships among the microbial species that determine microbial network per cluster of individuals. The results of our study suggest that there are several differences in microbial interactions on personalized network level in healthy oral samples acquired from various niches. Based on the results of co-regularized spectral clustering we discover two groups of individuals with different topology of their microbial interaction network. The results of microbial network inference suggest that niche-wise interactions are different in these two groups. Our study shows that healthy individuals have different microbial clusters according to their oral microbiota. Such personalized microbial networks open a better understanding of the microbial ecology of healthy oral cavities and new possibilities for future targeted medication. The scripts written in scientific Python and in Matlab, which were used for network visualization, are provided for download on the website http://learning-machines.com/. Copyright © 2015 Elsevier Inc. All rights reserved.
Combining a popularity-productivity stochastic block model with a discriminative-content model for general structure detection.

PubMed

Chai, Bian-fang; Yu, Jian; Jia, Cai-Yan; Yang, Tian-bao; Jiang, Ya-wen

2013-07-01

Latent community discovery that combines links and contents of a text-associated network has drawn more attention with the advance of social media. Most of the previous studies aim at detecting densely connected communities and are not able to identify general structures, e.g., bipartite structure. Several variants based on the stochastic block model are more flexible for exploring general structures by introducing link probabilities between communities. However, these variants cannot identify the degree distributions of real networks due to a lack of modeling of the differences among nodes, and they are not suitable for discovering communities in text-associated networks because they ignore the contents of nodes. In this paper, we propose a popularity-productivity stochastic block (PPSB) model by introducing two random variables, popularity and productivity, to model the differences among nodes in receiving links and producing links, respectively. This model has the flexibility of existing stochastic block models in discovering general community structures and inherits the richness of previous models that also exploit popularity and productivity in modeling the real scale-free networks with power law degree distributions. To incorporate the contents in text-associated networks, we propose a combined model which combines the PPSB model with a discriminative model that models the community memberships of nodes by their contents. We then develop expectation-maximization (EM) algorithms to infer the parameters in the two models. Experiments on synthetic and real networks have demonstrated that the proposed models can yield better performances than previous models, especially on networks with general structures.
Combining a popularity-productivity stochastic block model with a discriminative-content model for general structure detection

NASA Astrophysics Data System (ADS)

Chai, Bian-fang; Yu, Jian; Jia, Cai-yan; Yang, Tian-bao; Jiang, Ya-wen

2013-07-01

Latent community discovery that combines links and contents of a text-associated network has drawn more attention with the advance of social media. Most of the previous studies aim at detecting densely connected communities and are not able to identify general structures, e.g., bipartite structure. Several variants based on the stochastic block model are more flexible for exploring general structures by introducing link probabilities between communities. However, these variants cannot identify the degree distributions of real networks due to a lack of modeling of the differences among nodes, and they are not suitable for discovering communities in text-associated networks because they ignore the contents of nodes. In this paper, we propose a popularity-productivity stochastic block (PPSB) model by introducing two random variables, popularity and productivity, to model the differences among nodes in receiving links and producing links, respectively. This model has the flexibility of existing stochastic block models in discovering general community structures and inherits the richness of previous models that also exploit popularity and productivity in modeling the real scale-free networks with power law degree distributions. To incorporate the contents in text-associated networks, we propose a combined model which combines the PPSB model with a discriminative model that models the community memberships of nodes by their contents. We then develop expectation-maximization (EM) algorithms to infer the parameters in the two models. Experiments on synthetic and real networks have demonstrated that the proposed models can yield better performances than previous models, especially on networks with general structures.
Using Pathfinder networks to discover alignment between expert and consumer conceptual knowledge from online vaccine content.

PubMed

Amith, Muhammad; Cunningham, Rachel; Savas, Lara S; Boom, Julie; Schvaneveldt, Roger; Tao, Cui; Cohen, Trevor

2017-10-01

This study demonstrates the use of distributed vector representations and Pathfinder Network Scaling (PFNETS) to represent online vaccine content created by health experts and by laypeople. By analyzing a target audience's conceptualization of a topic, domain experts can develop targeted interventions to improve the basic health knowledge of consumers. The underlying assumption is that the content created by different groups reflects the mental organization of their knowledge. Applying automated text analysis to this content may elucidate differences between the knowledge structures of laypeople (heath consumers) and professionals (health experts). This paper utilizes vaccine information generated by laypeople and health experts to investigate the utility of this approach. We used an established technique from cognitive psychology, Pathfinder Network Scaling to infer the structure of the associational networks between concepts learned from online content using methods of distributional semantics. In doing so, we extend the original application of PFNETS to infer knowledge structures from individual participants, to infer the prevailing knowledge structures within communities of content authors. The resulting graphs reveal opportunities for public health and vaccination education experts to improve communication and intervention efforts directed towards health consumers. Our efforts demonstrate the feasibility of using an automated procedure to examine the manifestation of conceptual models within large bodies of free text, revealing evidence of conflicting understanding of vaccine concepts among health consumers as compared with health experts. Additionally, this study provides insight into the differences between consumer and expert abstraction of domain knowledge, revealing vaccine-related knowledge gaps that suggest opportunities to improve provider-patient communication. Copyright © 2017 Elsevier Inc. All rights reserved.
Optimal design of gene knockout experiments for gene regulatory network inference

PubMed Central

Ud-Dean, S. M. Minhaz; Gunawan, Rudiyanto

2016-01-01

Motivation: We addressed the problem of inferring gene regulatory network (GRN) from gene expression data of knockout (KO) experiments. This inference is known to be underdetermined and the GRN is not identifiable from data. Past studies have shown that suboptimal design of experiments (DOE) contributes significantly to the identifiability issue of biological networks, including GRNs. However, optimizing DOE has received much less attention than developing methods for GRN inference. Results: We developed REDuction of UnCertain Edges (REDUCE) algorithm for finding the optimal gene KO experiment for inferring directed graphs (digraphs) of GRNs. REDUCE employed ensemble inference to define uncertain gene interactions that could not be verified by prior data. The optimal experiment corresponds to the maximum number of uncertain interactions that could be verified by the resulting data. For this purpose, we introduced the concept of edge separatoid which gave a list of nodes (genes) that upon their removal would allow the verification of a particular gene interaction. Finally, we proposed a procedure that iterates over performing KO experiments, ensemble update and optimal DOE. The case studies including the inference of Escherichia coli GRN and DREAM 4 100-gene GRNs, demonstrated the efficacy of the iterative GRN inference. In comparison to systematic KOs, REDUCE could provide much higher information return per gene KO experiment and consequently more accurate GRN estimates. Conclusions: REDUCE represents an enabling tool for tackling the underdetermined GRN inference. Along with advances in gene deletion and automation technology, the iterative procedure brings an efficient and fully automated GRN inference closer to reality. Availability and implementation: MATLAB and Python scripts of REDUCE are available on www.cabsel.ethz.ch/tools/REDUCE. Contact: rudi.gunawan@chem.ethz.ch Supplementary information: Supplementary data are available at Bioinformatics online. PMID:26568633
Quantum Graphical Models and Belief Propagation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leifer, M.S.; Perimeter Institute for Theoretical Physics, 31 Caroline Street North, Waterloo Ont., N2L 2Y5; Poulin, D.

Belief Propagation algorithms acting on Graphical Models of classical probability distributions, such as Markov Networks, Factor Graphs and Bayesian Networks, are amongst the most powerful known methods for deriving probabilistic inferences amongst large numbers of random variables. This paper presents a generalization of these concepts and methods to the quantum case, based on the idea that quantum theory can be thought of as a noncommutative, operator-valued, generalization of classical probability theory. Some novel characterizations of quantum conditional independence are derived, and definitions of Quantum n-Bifactor Networks, Markov Networks, Factor Graphs and Bayesian Networks are proposed. The structure of Quantum Markovmore » Networks is investigated and some partial characterization results are obtained, along the lines of the Hammersley-Clifford theorem. A Quantum Belief Propagation algorithm is presented and is shown to converge on 1-Bifactor Networks and Markov Networks when the underlying graph is a tree. The use of Quantum Belief Propagation as a heuristic algorithm in cases where it is not known to converge is discussed. Applications to decoding quantum error correcting codes and to the simulation of many-body quantum systems are described.« less
Semantic message oriented middleware for publish/subscribe networks

NASA Astrophysics Data System (ADS)

Li, Han; Jiang, Guofei

2004-09-01

The publish/subscribe paradigm of Message Oriented Middleware provides a loosely coupled communication model between distributed applications. Traditional publish/subscribe middleware uses keywords to match advertisements and subscriptions and does not support deep semantic matching. To this end, we designed and implemented a Semantic Message Oriented Middleware system to provide such capabilities for semantic description and matching. We adopted the DARPA Agent Markup Language and Ontology Inference Layer, a formal knowledge representation language for expressing sophisticated classifications and enabling automated inference, as the topic description language in our middleware system. A simple description logic inference system was implemented to handle the matching process between the subscriptions of subscribers and the advertisements of publishers. Moreover our middleware system also has a security architecture to support secure communication and user privilege control.
Estimation of dew point temperature using neuro-fuzzy and neural network techniques

NASA Astrophysics Data System (ADS)

Kisi, Ozgur; Kim, Sungwon; Shiri, Jalal

2013-11-01

This study investigates the ability of two different artificial neural network (ANN) models, generalized regression neural networks model (GRNNM) and Kohonen self-organizing feature maps neural networks model (KSOFM), and two different adaptive neural fuzzy inference system (ANFIS) models, ANFIS model with sub-clustering identification (ANFIS-SC) and ANFIS model with grid partitioning identification (ANFIS-GP), for estimating daily dew point temperature. The climatic data that consisted of 8 years of daily records of air temperature, sunshine hours, wind speed, saturation vapor pressure, relative humidity, and dew point temperature from three weather stations, Daego, Pohang, and Ulsan, in South Korea were used in the study. The estimates of ANN and ANFIS models were compared according to the three different statistics, root mean square errors, mean absolute errors, and determination coefficient. Comparison results revealed that the ANFIS-SC, ANFIS-GP, and GRNNM models showed almost the same accuracy and they performed better than the KSOFM model. Results also indicated that the sunshine hours, wind speed, and saturation vapor pressure have little effect on dew point temperature. It was found that the dew point temperature could be successfully estimated by using T mean and R H variables.

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